protocol_id stringclasses 263
values | section_number stringlengths 1 12 | title stringlengths 1 1.88k | content stringlengths 0 866k | merged_titles listlengths 0 491 |
|---|---|---|---|---|
NCT03167242 | 1.2 | Purpose | 1.2 Purpose This Phase 2 study aims to determine the most effective and tolerable dose at the shortest dosing regimen of the investigational drug KAF156 and a Solid Dispersion Formulation of lumefantrine (LUM-SDF) in combination in adult/adolescent and pediatric patients with uncomplicated P. falciparum malaria. Differ... | [] |
NCT03167242 | 2 | Study objectives and endpoints | 2 Study objectives and endpoints | [] |
NCT03167242 | 2.1 | Objectives and related endpoints | 2.1 Objectives and related endpoints Table 2-1 Objectives and related endpoints (PK Run-in Part, Part A and Part B) | Objective(s) | Endpoint (s) | | | |--------------------------------------------------------------------------------|------------------------------------------------------------------------------------|-... | [
"Objective(s) Endpoint (s)",
"Secondary Objective(s)",
"Endpoint(s) for secondary objective(s)"
] |
NCT03167242 | 3 | Investigational plan | 3 Investigational plan | [] |
NCT03167242 | 3.1 | Study design | 3.1 Study design This will be a multicenter, open-label, randomized, parallel-group study in adults and children with confirmed and uncomplicated P. falciparum malaria. Screening of patients for inclusion in the study consists of two parts: a Pre-Screening Part and a Screening Part. - Pre-Screening Part (Study Visit 1)... | [
"PK Run-in Part;",
"Part A:",
"Part B:"
] |
NCT03167242 | 3.2 | Rationale for study design | 3.2 Rationale for study design This will be a multicenter, open-label, randomized, parallel-group study in adults and children with confirmed and uncomplicated P. falciparum malaria. The use of a combination regimen with two drugs is well established for evaluation of antimalaria therapy and is recommended by WHO guide... | [] |
NCT03167242 | 3.3 | Rationale for dose/regimen, route of administration and duration of treatment | 3.3 Rationale for dose/regimen, route of administration and duration of treatment
Rationale for dose/regimen in PK Run-in Part: The objective of the PK Run-in cohort is to assess the maximum potential increase in KAF156 exposure as victim due to LUM-SDF with sufficient safety margins. Therefore, the lowest dose of KAF... | [
"Rationale for dose/regimen in PK Run-in Part:",
"Rationale for dose/regimen in Part A:",
"Rationale for dose/regimen in Part B:",
"Rationale for duration of treatment:"
] |
NCT03167242 | 3.4 | Rationale for choice of control | 3.4 Rationale for choice of control The control treatment used in Parts A and B of this study is Coartem®, the artemisinin-based combination therapy artemether-lumefantrine. Coartem® is widely used for P. falciparum malaria and has a well-characterized safety and efficacy profile [\(Hamed and Grueninger 2012](#page-84-... | [] |
NCT03167242 | 3.5 | Purpose and timing of interim assessments/data reviews | 3.5 Purpose and timing of interim assessments/data reviews For the PK Run-in Part the first 24 hours of PK samples will be analyzed for KAF156 and lumefantrine blood levels in order to confirm doses of KAF156 for Part A. In case of unexpected increase in exposure of KAF156 doses in Part A will be adjusted according to ... | [] |
NCT03167242 | 3.6 | Risks and benefits | 3.6 Risks and benefits Based on the preclinical and clinical evaluation to date as presented in the respective Investigator Brochures (IB) for KAF156 and LUM-SDF, the combination of KAF156 and LUM-SDF is expected to be generally safe and well tolerated. The risk to patients in this trial will be minimized by compliance... | [] |
NCT03167242 | 4 | Population | 4 Population The study population will consist of male and female patients (PK Run-in Part and Part A: ≥ 12 years old and ≥ 35.0 kg; Part B: 2 to < 12 years old and ≥ 10.0 kg) with confirmed and uncomplicated P. falciparum malaria. Only patients with malaria symptoms and P. falciparum counts more than 1000 and less tha... | [] |
NCT03167242 | 4.1 | Inclusion criteria | 4.1 Inclusion criteria Patients eligible for inclusion in this study must fulfill all of the following criteria:
Demography 1. PK Run-in Part and Part A: male and female patients ≥ 12 years and with a body weight ≥ 35.0 kg Part B: after determining the effective/tolerated doses and regimens in adolescent and adult pat... | [
"Demography",
"Regulations"
] |
NCT03167242 | 4.2 | Exclusion criteria | 4.2 Exclusion criteria Patients fulfilling any of the following criteria are not eligible for inclusion in this study. No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible patients.
Medical history and clinical status - 1. Mixe... | [
"Medical history and clinical status",
"Interfering substances",
"Specific to the study"
] |
NCT03167242 | 5 | Treatment | 5 Treatment | [] |
NCT03167242 | 5.1 | Study treatment | 5.1 Study treatment | [] |
NCT03167242 | 5.1.1 | Investigational and control drugs | 5.1.1 Investigational and control drugs Novartis will supply the following investigational products as open label patient specific supplies (see [Table 5-1](#page-34-0), [Table 5-3](#page-34-0), [Table 5-4](#page-35-0) and [Appendix 5\)](#page-92-0). - For PK Run-in Part: - KAF156 50 mg and/or 100 mg and/or 200 mg (Tab... | [
"For Part A:",
"For Part B:"
] |
NCT03167242 | 5.1.2 | Additional treatment | 5.1.2 Additional treatment No additional treatment beyond investigational drug and control drug are included in this trial. Rescue medication will be provided by the investigator according to local practices ([Section 5.6.6\)](#page-40-0). | [] |
NCT03167242 | 5.2 | Treatment arms | 5.2 Treatment arms Following confirmation of exposure in the PK Run-in Part, patients will be randomized in 2:2:2:2:2:2:1 ratios between six KAF156 and LUM-SDF dose combinations and the Coartem® cohort in Part A. In Part B, patients will be randomized in 2:1 ratios (2 for each KAF156 and LUM-SDF dose combination and 1 ... | [
"PK Run-in Part (≥ 12 years old, ≥ 35.0 kg):",
"Part A (≥ 12 years old, ≥ 35.0 kg)\\:",
"Part B (2 to < 12 years, ≥ 10.0 kg):"
] |
NCT03167242 | 5.3 | Treatment assignment and randomization | 5.3 Treatment assignment and randomization
PK Run-in Part At Visit 101, the investigator or his/her delegate will contact the IRT after confirming that a patient fulfills all the inclusion/exclusion criteria. If the enrollment for this part is still open, the eligible patient will be assigned to receive KAF156 200 mg ... | [
"PK Run-in Part",
"Parts A and B"
] |
NCT03167242 | 5.4 | Treatment blinding | 5.4 Treatment blinding | [] |
NCT03167242 | 5.4.1 | PK Run-in Part | 5.4.1 PK Run-in Part Treatment blinding in the PK Run-in Part is not applicable since the part is a single cohort. | [] |
NCT03167242 | 5.4.2 | Parts A and B | 5.4.2 Parts A and B Treatment will not be blinded to patients and investigators since dose frequency and dosages for KAF156 and LUM-SDF may change from cohort to cohort and double-blinding will require triple dummies for 3 different drugs (KAF156, LUM-SDF, and Coartem®). Double-blinding is further complicated by the fo... | [] |
NCT03167242 | 5.5 | Transition from PK Run-in Part to Part A and from Part A to Part B | 5.5 Transition from PK Run-in Part to Part A and from Part A to Part B Following the PK results from the PK Run-in cohort, the sponsor will set up IRT/dosing of KAF156 for Part A as specified in [Table 3-1](#page-27-0) and [Appendix 5](#page-92-0). All investigators will be informed accordingly. After completion of Par... | [] |
NCT03167242 | 5.6 | Treating the patient | 5.6 Treating the patient Sponsor qualified medical personnel will be readily available to advise on trial related medical questions or problems. | [] |
NCT03167242 | 5.6.1 | Patient numbering | 5.6.1 Patient numbering Each patient is uniquely identified by a Subject Number which is composed by the site number assigned by Novartis and a sequential number assigned by the investigator. Once assigned to a patient, the Subject Number will not be reused. Upon signing the pre-screening informed consent form, the pat... | [] |
NCT03167242 | 5.6.2 | Dispensing the study drug | 5.6.2 Dispensing the study drug Each study site will be supplied with study drugs in individual packaging for each patient. The study drug packaging has a 2-part label. A unique medication number is printed on each part of this label which corresponds to one of the treatment drugs and dose. Investigator staff will iden... | [] |
NCT03167242 | 5.6.3 | Handling of study treatment | 5.6.3 Handling of study treatment Study treatment must be received by a designated person at the study site, handled and stored safely and properly, and kept in a secured location to which only the investigator and designees have access. Upon receipt, all study treatment must be stored according to the instructions spe... | [] |
NCT03167242 | 5.6.4 | Instructions for prescribing and taking study treatment KAF156 and LUM-SDF | 5.6.4 Instructions for prescribing and taking study treatment KAF156 and LUM-SDF Patients must be fasted 3 hours before and 4 hours after KAF156/LUM-SDF administration. Water can be provided ad-libitum. In Part B, pediatric patients may be given non-fatty liquids such as orange juices prior to 1 hour of dosing and 1 ho... | [
"Coartem®"
] |
NCT03167242 | 5.6.5 | Permitted dose adjustments and interruptions of study treatment | 5.6.5 Permitted dose adjustments and interruptions of study treatment No dose adjustments other than according to body weight group as described above (see [Section](#page-33-0) [5.1.1\)](#page-33-0) are permitted. Additional doses can be given in case of vomiting (see [Section 5.6.4](#page-39-0)). The changes must be ... | [] |
NCT03167242 | 5.6.6 | Rescue medication | 5.6.6 Rescue medication The following circumstances warrant discontinuation of study treatment and the implementation of rescue medication (see [Section 6.5.8](#page-59-0)):
Early Treatment Failure (ETF) - Development of danger signs or severe malaria on Day 2, Day 3, Day 4 in the presence of parasitaemia. - Parasitae... | [
"Early Treatment Failure (ETF)",
"Late Clinical Failure (LCF)",
"Late Parasitological Failure (LPF)"
] |
NCT03167242 | 5.6.7 | Prior and Concomitant medication | 5.6.7 Prior and Concomitant medication Prior medications are defined as drugs taken and stopped prior to first dose of study medication. Concomitant medication is defined as any medication, other than the Investigational Medicinal Product (IMP), which is given at least once between the day of first dose of randomized s... | [] |
NCT03167242 | 5.6.8 | Prohibited medication | 5.6.8 Prohibited medication | [] |
NCT03167242 | 5.6.8.1 | Drug with potential impact on efficacy & safety | 5.6.8.1 Drug with potential impact on efficacy & safety Drugs with antimalarial effect: Drugs/supplements which are known to have antimalarial effects are NOT allowed within minimum of their five (5) plasma half-lives (or minimum of 4 weeks if half-life is unknown) prior to enrollment and during the entire study period... | [] |
NCT03167242 | 5.6.8.2 | Drug with potential for pharmacokinetic interaction: | 5.6.8.2 Drug with potential for pharmacokinetic interaction: Drugs/supplements impacting KAF156 and lumefantrine exposure: drugs or supplements which are known CYP3A inhibitors (e.g., erythromycin, ketoconazole, itraconazole, cimetidine) or CYP3A inducers (e.g. rifampin, phenobarbital) etc. should not be used during st... | [] |
NCT03167242 | 5.7 | Study completion and discontinuation | 5.7 Study completion and discontinuation | [] |
NCT03167242 | 5.7.1 | Study completion and post-study treatment | 5.7.1 Study completion and post-study treatment Each patient will be required to complete the study in its entirety and thereafter no further study treatment will be made available to them. A patient will be considered to have completed the study when the patient has completed the last visit planned in the protocol, an... | [] |
NCT03167242 | 5.7.2 | Discontinuation of study treatment | 5.7.2 Discontinuation of study treatment Patients will be treated under hospital supervision during the treatment period. Discontinuation of study treatment for a patient occurs when study drug is stopped earlier than the protocol b CYP substrates with narrow therapeutic range refers to drugs whose exposure-response re... | [] |
NCT03167242 | 5.7.3 | Premature Study Withdrawal | 5.7.3 Premature Study Withdrawal Patients are considered to be withdrawn prematurely from the study if they do not complete the follow-up visits until Day 43. A patient may voluntarily discontinue participation in this study at any time. The investigator may also, at their discretion, discontinue the patient from parti... | [] |
NCT03167242 | 5.7.4 | Withdrawal of informed consent | 5.7.4 Withdrawal of informed consent Patients may voluntarily withdraw consent to participate in the study for any reason at any time. Withdrawal of consent (WoC) from the study is defined as when a patient: Does not want to participate in the study anymore and/or Does not want any further visits or assessments and/or ... | [] |
NCT03167242 | 5.7.5 | Loss to follow-up | 5.7.5 Loss to follow-up For subjects whose status is unclear because they fail to appear for study visits without stating an intention to discontinue or withdraw, the investigator must show "due diligence" by documenting in the source documents steps taken to contact the subject, e.g. dates of telephone calls, register... | [] |
NCT03167242 | 5.7.6 | Early study termination by the sponsor | 5.7.6 Early study termination by the sponsor The study can be terminated by Novartis at any time for any reason. This may include reasons related to the benefit risk assessment of participating in the study, practical reasons, or for regulatory or medical reasons (including slow enrolment). Should this be necessary, th... | [] |
NCT03167242 | 6 | Visit schedule and assessments | 6 Visit schedule and assessments Patients must be seen for all visits on the designated day, or as close to it as possible. Missed or rescheduled visits should not lead to automatic discontinuation. Patients who prematurely discontinue the study for any reason should be scheduled for a visit as soon as possible, at whi... | [] |
NCT03167242 | 6.1 | Information to be collected on screening failures | 6.1 Information to be collected on screening failures All patients/subjects who have signed informed consent but not entered into the next epoch/period will have the study completion page for the screening epoch/period, demographics, inclusion/exclusion, and serious adverse event (SAE) data collected. Adverse events th... | [] |
NCT03167242 | 6.2 | Patient demographics/other baseline characteristics | 6.2 Patient demographics/other baseline characteristics Patient demographic and baseline characteristic data to be collected on all patients include: - Age - Gender - Body weight - Body height - Body temperature - Initial medical and treatment history - Severe malaria - Vital signs - Physical exam - Prior and concomita... | [] |
NCT03167242 | 6.3 | Treatment exposure and compliance | 6.3 Treatment exposure and compliance Compliance will be assessed by the investigator and/or study personnel at each visit using pill/sachet counts. This information should be captured in the source document at each visit. All study treatment taken must be recorded in the Dosage Administration Record CRF, along with an... | [] |
NCT03167242 | 6.4 | Efficacy | 6.4 Efficacy Efficacy assessments will be based on the PCR-corrected Adequate Clinical and Parasitological Response (ACPR) at Day 29 (see [Section 6.5.8](#page-59-0)). | [] |
NCT03167242 | 6.4.1 | Parasitaemia assessment (details provided in the laboratory manual) | 6.4.1 Parasitaemia assessment (details provided in the laboratory manual) Blood sampling for parasitology can be done by means of finger prick except when the timing for parasitology assessments coincide with time for clinical laboratory tests, in which case, blood sample can be taken from the venous blood collected fo... | [] |
NCT03167242 | 6.4.3 | Blood sample for molecular diagnostic purposes | 6.4.3 Blood sample for molecular diagnostic purposes Blood will be sampled for parasite genotyping as indicated in the assessment schedule ([Table](#page-48-0) [6-1\)](#page-48-0). At screening, blood sample will be collected in all patients fulfilling eligibility criteria for inclusion in the study. A second blood sam... | [] |
NCT03167242 | 6.4.4 | Appropriateness of efficacy assessments | 6.4.4 Appropriateness of efficacy assessments The microscopy examination methods to quantify the malaria parasite and gametocyte in blood are validated methods [\(Sinden et al](#page-84-0) 2012; [White et al](#page-84-0) 2014). For full details refer to the Study Laboratory Procedures Manual. | [] |
NCT03167242 | 6.5 | Safety | 6.5 Safety Clinical adverse events will be monitored throughout the study to assess the general safety and tolerability of the treatment groups. | [] |
NCT03167242 | 6.5.1 | Physical examination and malaria signs and symptoms | 6.5.1 Physical examination and malaria signs and symptoms A complete physical examination will be performed by the investigational staff at screening and include the examination of general appearance, skin, neck (including thyroid), eyes, ears, nose, throat, lungs, heart, abdomen including splenomegaly, back, lymph nod... | [] |
NCT03167242 | 6.5.2 | Vital signs | 6.5.2 Vital signs Vital signs (blood pressure, body pulse) will be monitored as part of the physical exam as indicated in the study assessment schedule table and recorded on the clinical database. After the patient has been in supine position for five minutes, systolic and diastolic blood pressure will be measured thre... | [] |
NCT03167242 | 6.5.3 | Body temperature | 6.5.3 Body temperature Body temperature will be monitored as indicated in the study assessment schedule table and recorded on the clinical data base. Fever monitoring will be done every 6 hours until resolution of fever, defined as being afebrile for 24 hours. Fever Clearance is defined (in patients with an increased t... | [] |
NCT03167242 | 6.5.4 | Laboratory evaluations | 6.5.4 Laboratory evaluations A local laboratory will be preferably used for analysis of all specimens collected except for PCR (parasite identification and resistance markers), ECG and PK measurements where central laboratory will be used. Details on the collections, shipment of samples and reporting of results by the ... | [] |
NCT03167242 | 6.5.4.1 | Hematology | 6.5.4.1 Hematology Hemoglobin, hematocrit (packed-cell volume - PCV), white blood cell (WBC) count with differential (as much as possible, neutrophil, lymphocyte and eosinophils counts will be performed while basophils and monocytes can be aggregated as 'other'). Red blood cell count (RBC), reticulocytes count and hapt... | [] |
NCT03167242 | 6.5.4.2 | Blood chemistry | 6.5.4.2 Blood chemistry Routine blood chemistry testing will be performed according to the visit schedule in order to monitor the general medical condition of the patient. This includes: Glucose, creatinine (serum), transaminases (ALT/SGPT and AST/SGOT), serum-γ-glutamyl transferase (GGT), Total and conjugated bilirubi... | [] |
NCT03167242 | 6.5.4.3 | Urinalysis | 6.5.4.3 Urinalysis Dipstick measurements for specific gravity, protein, glucose and blood will be performed as indicated in the study assessment schedule table. Microscopy will be performed and urine sediment will be assessed in case of an abnormal dipstick test. | [] |
NCT03167242 | 6.5.5 | Electrocardiogram (ECG) | 6.5.5 Electrocardiogram (ECG) ECGs should be taken in triplicate within 5 minutes (after 10 minutes rest in the supine position to ensure a stable heart rate according to the ECG investigator manual). The preferred sequence of cardiovascular data collection during study visits is ECG collection first, followed by vital... | [] |
NCT03167242 | 6.5.6 | Pregnancy and assessments of fertility | 6.5.6 Pregnancy and assessments of fertility A pregnancy test in urine will be performed at the screening visit and at study completion. Any female aged 8 years and above is considered a woman of child-bearing potential (WOCBP), and must be included among female patients undergoing obligatory pregnancy testing during t... | [] |
NCT03167242 | 6.5.7 | Appropriateness of safety measurements | 6.5.7 Appropriateness of safety measurements The safety assessments selected are standard for this indication/patient population. | [] |
NCT03167242 | 6.5.8 | WHO definition | 6.5.8 WHO definition
Definition of treatment failures
Early Treatment Failures (ETF) - Development of danger signs or severe malaria on Day 2, Day 3, Day 4 in the presence of parasitaemia. - Parasitaemia on Day 3 higher than Day 1 count irrespective of axillary temperature. - Parasitaemia on Day 4 with axillary tempe... | [
"Definition of treatment failures",
"Early Treatment Failures (ETF)",
"Development of danger signs or severe malaria on any day from Day 5 to Day 43 in the presence of parasitaemia without previously meeting any of the criteria of early treatment",
"Late Parasitological Failure (LPF)",
"Adequate Clinical an... |
NCT03167242 | 7 | Safety monitoring | 7 Safety monitoring | [] |
NCT03167242 | 7.1 | Adverse events | 7.1 Adverse events An adverse event (AE) is any untoward medical occurrence (e.g., any unfavorable and unintended sign (including abnormal laboratory findings), symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study until the end of stu... | [] |
NCT03167242 | 7.2 | Serious adverse events | 7.2 Serious adverse events | [] |
NCT03167242 | 7.2.1 | Definition of SAE | 7.2.1 Definition of SAE An SAE is defined as any adverse event (appearance of (or worsening of any pre-existing)) undesirable sign(s), symptom(s) or medical conditions(s)) which meets any one of the following criteria: - is fatal or life-threatening - results in persistent or significant disability/incapacity - constit... | [
"Expectedness assessment"
] |
NCT03167242 | 7.2.2 | SAE reporting | 7.2.2 SAE reporting To ensure patient safety, every SAE, regardless of causality, occurring after the patient has provided informed consent and until 30 days after the last study visit must be reported to Novartis safety within 24 hours of learning of its occurrence. Any SAEs experienced after the 30 day period after t... | [] |
NCT03167242 | 7.3 | Liver safety monitoring | 7.3 Liver safety monitoring To ensure patient safety and enhance reliability in determining the hepatotoxic potential of an investigational drug, a standardized process for identification, monitoring and evaluation of liver events has to be followed. The following two categories of abnormalities/adverse events have to ... | [] |
NCT03167242 | 7.4 | Renal safety monitoring | 7.4 Renal safety monitoring The following two categories of abnormal renal laboratory values have to be considered during the course of the study: - Serum event: - confirmed (after ≥ 24h) increase in serum creatinine of ≥ 25% compared to baseline during normal hydration status - Urine event - new onset (≥ 1+) proteinur... | [] |
NCT03167242 | 7.5 | Cardiac Safety Monitoring | 7.5 Cardiac Safety Monitoring To ensure patient safety and fully characterize the cardiovascular safety of the investigational drug, a standardized process for identification, monitoring and evaluation of cardiac events is followed. The following categories of notable ECG changes will be assessed during the course of t... | [] |
NCT03167242 | 7.6 | Reporting of study treatment errors including misuse/abuse | 7.6 Reporting of study treatment errors including misuse/abuse Medication errors are unintentional errors in the prescribing, dispensing, administration or monitoring of a medicine while under the control of a healthcare professional, patient or consumer (European Medicines Agency (EMA) definition). Misuse refers to si... | [] |
NCT03167242 | 7.7 | Pregnancy reporting | 7.7 Pregnancy reporting To ensure patient safety, each pregnancy occurring after signing the informed consent must be reported to Novartis within 24 hours of learning of its occurrence. The pregnancy should be followed up to determine outcome, including spontaneous or voluntary termination, details of the birth, and th... | [] |
NCT03167242 | 8 | Data review and database management | 8 Data review and database management | [] |
NCT03167242 | 8.1 | Site monitoring | 8.1 Site monitoring Before study initiation, at a site initiation visit or at an investigator's meeting, a Novartis representative will review the protocol and eCRFs with the investigators and their staff. During the study, the field monitor will visit the site regularly to check the completeness of patient records, th... | [] |
NCT03167242 | 8.2 | Data collection | 8.2 Data collection Designated investigator staff will enter the data required by the protocol into the Electronic Case Report Forms using fully validated software that conforms to 21 US Code of Federal Regulations (CFR) Part 11 requirements. Designated investigator site staff will not be given access to the EDC system... | [] |
NCT03167242 | 8.3 | Data management and quality control | 8.3 Data management and quality control Novartis staff (or Contract Research Organization (CRO) working on behalf of Novartis) review the data entered into the CRFs by investigational staff for completeness and accuracy and instruct the site personnel to make any required corrections or additions. Queries are sent to t... | [] |
NCT03167242 | 8.4 | Data Monitoring Committee | 8.4 Data Monitoring Committee An independent Data Monitoring Committee (DMC) will be established for this study to review patient safety at several time points. The DMC can recommend to stop the study or a specific cohort in case of serious safety observations which can include a non-acceptable rate of early treatment ... | [] |
NCT03167242 | 9 | Data analysis | 9 Data analysis Statistical analyses for PK Run-in Part, Part A and Part B will be performed separately. For key efficacy and safety outcomes, pooled analysis will be performed by pooling Part B with corresponding cohorts in Part A. Unless described separately otherwise, same statistical method will be used for separat... | [] |
NCT03167242 | 9.1 | Analysis sets | 9.1 Analysis sets
Randomized set All patients who are randomized.
Full analysis set (FAS) FAS will be comprised of all patients from Randomized set who take at least one dose of study treatment during the treatment period and whose baseline parasitaemia count is greater than 0. Following the intent-to-treat principle... | [
"Randomized set",
"Full analysis set (FAS)",
"Safety set (SS)",
"Per-protocol set (PPS)",
"PK analysis set"
] |
NCT03167242 | 9.2 | Patient demographics and other baseline characteristics | 9.2 Patient demographics and other baseline characteristics Demographic data and baseline disease characteristics will be descriptively presented and tabulated (n, mean, standard deviation, median, minimum, and maximum for continuous variables; n and percent for categorical variables) per treatment group, as well as ov... | [] |
NCT03167242 | 9.3 | Treatments | 9.3 Treatments All analyses in this section will be performed using the safety set. | [] |
NCT03167242 | 9.3.1 | Study treatment | 9.3.1 Study treatment Number and percentage of doses taken will be presented by treatment group and drug (KAF156, LUM-SDF, or Coartem®). The percentage will be calculated based on the planned number of doses per treatment group. Percentage of patients with study drug vomiting and dose replacement will be presented by t... | [] |
NCT03167242 | 9.3.2 | Prior and concomitant medication | 9.3.2 Prior and concomitant medication Medications will be identified using the Novartis drug and therapy dictionary (NovDTD) including Anatomical Therapeutic Chemical (ATC) code. Prior and concomitant medications will be summarized by treatment group in separate tables. Concomitant rescue and other anti-malarial medic... | [] |
NCT03167242 | 9.4 | Analysis of the primary variable(s) | 9.4 Analysis of the primary variable(s) The PK Run-in Part will be separately analyzed. The primary objective for the PK Run-in Part is to investigate the pharmacokinetic interaction potential between KAF156 and LUM-SDF. The analyses of PK parameters of KAF156 and LUM-SDF are detailed in [Section 9.5.4](#page-77-0). Th... | [] |
NCT03167242 | 9.4.1 | Primary Variable(s) | 9.4.1 Primary Variable(s) The primary efficacy variable is the PCR corrected Adequate Clinical and Parasitological Response (ACPR) at Day 29. A patient is considered as PCR-corrected ACPR at Day 29 if the patient does not meet any of the criteria of early treatment failure (up to Day 4), late clinical failure (Day 5 to... | [] |
NCT03167242 | 9.4.2 | Statistical model, hypothesis, and method of analysis | 9.4.2 Statistical model, hypothesis, and method of analysis The statistical null hypothesis is that the ACPR rate at Day 29 is at most 80% with the alternative hypothesis that the ACPR rate at Day 29 is greater than 80%. The statistical hypothesis will be evaluated using the lower limit of 2-sided 95% exact confidence ... | [] |
NCT03167242 | 9.4.3 | Handling of missing values/censoring/discontinuations | 9.4.3 Handling of missing values/censoring/discontinuations No missing data are expected for the primary efficacy analysis based on PPS since patients who are not evaluable for the primary efficacy variable are excluded from PPS. See [Section 9.4.4](#page-73-0) for missing data handling for the supportive analysis usin... | [] |
NCT03167242 | 9.4.4 | Sensitivity analyses | 9.4.4 Sensitivity analyses The primary efficacy variable will be performed based on the FAS using the statistical method specified in [Section 9.4.2.](#page-73-0) Missing primary efficacy variable will be handled as follows: - Patients who received rescue medication for the treatment of P. falciparum malaria (except fo... | [] |
NCT03167242 | 9.5 | Analysis of secondary variables | 9.5 Analysis of secondary variables | [] |
NCT03167242 | 9.5.1 | Efficacy variables | 9.5.1 Efficacy variables Secondary efficacy variables include: - 1. PCR-corrected ACPR at Days 15 and 43; - 2. Uncorrected ACPR at Days 15, 29, and 43; - 3. Proportion of patients with parasitaemia at 12, 24, and 48 hours after treatment; - 4. Time to parasite clearance (PCT), defined as time from the first dose until ... | [] |
NCT03167242 | 9.5.1.1 | PCR-corrected ACPR and uncorrected ACPR | 9.5.1.1 PCR-corrected ACPR and uncorrected ACPR At each visit, the mean ACPR rate with 95% confidence intervals will be provided using Pearson-Clopper method for each treatment group. Data will be handled as follows: - Treatment failures after 7 days (i.e., Day 8) due to reinfection based on PCR genotyping are not cons... | [] |
NCT03167242 | 9.5.1.2 | Treatment failure related parameters | 9.5.1.2 Treatment failure related parameters For the following parameters, 95% confidence intervals will be provided for each treatment group using the Pearson-Clopper method: - proportion of patients with parasitaemia at 12, 24, and 48 hours after treatment - proportion of patients with early treatment failure (ETF) -... | [] |
NCT03167242 | 9.5.1.3 | Parasite clearance time (PCT) and fever clearance time (FCT) | 9.5.1.3 Parasite clearance time (PCT) and fever clearance time (FCT) Descriptive statistics (mean, standard error, median, quartiles) will be presented using the Kaplan-Meier method. Kaplan-Meier curves will be provided. PCT will be calculated based on uncorrected parasite counts. Patients without parasite clearance fo... | [] |
NCT03167242 | 9.5.1.4 | Recrudescence and reinfection | 9.5.1.4 Recrudescence and reinfection Reinfection is defined as appearance of asexual parasites after clearance of initial infection with a genotype different from those parasites present at baseline. Reinfection must be confirmed by PCR analysis. Recrudescence is defined as appearance of asexual parasites after cleara... | [] |
NCT03167242 | 9.5.2 | Safety variables | 9.5.2 Safety variables All safety parameters will be analyzed based on the safety. | [] |
NCT03167242 | 9.5.2.1 | Adverse event | 9.5.2.1 Adverse event The number and percentage of patients who report adverse events will be summarized by treatment group according to primary system organ class (PSOC), preferred term, and severity. If a patient reports more than one adverse event with the same preferred term, the adverse event with the greatest sev... | [] |
NCT03167242 | 9.5.2.2 | Laboratory evaluations | 9.5.2.2 Laboratory evaluations Summary of laboratory evaluations will be presented with respect to three groups of laboratory tests (hematology, blood chemistry, and urinalysis). Descriptive summary statistics (mean, median, standard deviation, minimum and maximum) for the baseline, each study visit, and change from ba... | [] |
NCT03167242 | 9.5.2.3 | Vital signs | 9.5.2.3 Vital signs Descriptive summary statistics for the baseline, each study visit, and change from baseline to each study visit will be presented for each vital sign parameter (pulse rate, systolic/diastolic blood pressures) for each treatment group. Number and percentage of patients who have vital sign values that... | [] |
NCT03167242 | 9.5.2.4 | ECGs | 9.5.2.4 ECGs Descriptive summary statistics for the baseline, each study visit, and change from baseline to each study visit will be presented for heart rate, PR interval, QRS interval, RR interval, QT interval, QTcB (QT interval corrected for heart rate according to Bazett) and QTcF (QT interval corrected for heart ra... | [] |
NCT03167242 | 9.5.3 | Resource utilization | 9.5.3 Resource utilization Data relating to resource utilization will be used for the purpose of economic evaluation which will be carried out and reported as a separate activity. | [] |
NCT03167242 | 9.5.4 | Pharmacokinetics | 9.5.4 Pharmacokinetics PK concentrations below the limit of quantification will be treated as zero in summary statistics and for the calculation of pharmacokinetic parameters by non-compartmental analysis. Descriptive statistics of pharmacokinetic parameters will include arithmetic and geometric (means, standard deviat... | [] |
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