Health Condition 1: B95-B97- Bacterial and viral infectious agents
Conditions
Interventions
Intervention1: Part A: KAF156 400mg + LUM-SDF 960mg 1 Day oral dose
Intervention2: Part A: KAF156 800mg + LUM-SDF 960 mg 1 day oral
Intervention3: Part A: KAF156 400mg + LUM 960mg 2 days Oral
Interven
Sponsors
Novartis Healthcare Pvt Ltd
Eligibility
Inclusion criteria
Inclusion criteria: 1 PK Run-in Part and Part A: male and female patients â�¥ 12 years and with a body weight â�¥ 35.0 kg Part B: after determining the effective/tolerated doses and regimens in adolescent and adult patients, male and female patients â�¥ 2 and 2 Microscopic confirmation of P. falciparum by Giemsa-stained thick and thin films (refer to the laboratory manual for details) 3 P. falciparum parasitaemia of more than 1000 and less than 150 000 parasites/�µL at the time of pre-screening (i.e., Study Visit 1) 4 Axillary temperature â�¥ 37.5 �ºC or oral/tympanic/rectal temperature â�¥ 38.0�ºC; or similar history of fever during the previous 24 hours (history of fever must be documented) 5 Negative pregnancy test for women of child bearing potential (WOCBP) 6 Written informed consent must be obtained before any assessment is performed. If the patient is unable to read and write, then a witnessed consent according to local ethical standards is permitted. Patients 7 The patient or his/her parent/legal guardian (in case of pediatric patients) is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and is likely to complete the study as planned
Exclusion criteria
Exclusion criteria: 1 Mixed Plasmodium infections 2 Signs and symptoms of severe malaria according to WHO 2015 criteria unless characterized by high parasitaemia only 3 Patients with concurrent febrile illnesses (e.g., typhoid fever) 4 Active infections including tuberculosis 5 History of, or current alcohol misuse/abuse defined as five or more drinks on the same occasion on each of 5 or more days in the past 30 days 6 Known relevant liver disease e.g. chronic hepatitis, cirrhosis, compensated or decompensated, history of hepatitis B or C, hepatitis B or A vaccination in last 3 months, known gallbladder or bile duct disease, acute or chronic pancreatitis 7 Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection 8 Women of child bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for the duration of the study. Highly effective contraception methods include ïâ??· Total abstinence (when this is in line with the preferred and usual lifestyle of the patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) total hysterectomy or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment Male sterilization (at least 6 months prior to screening). For female patients on the study, the vasectomized male partner should be the sole partner for that patient 9 Active duodenal ulcer, ulcerative colitis, Crohnââ?¬•s disease, chronic (i.e., > 2 weeks) use of non-steroidal anti-inflammatory drugs (NSAIDs) 10 Clinically relevant abnormalities of electrolyte balance which require correction, e.g hypokalemia, hypocalcemia or hypomagnesemia.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of this study is to determine the effective doses of KAF156 combined with LUM-SDF given daily over 1, 2 or 3 days for treatment of uncomplicated malaria caused by P. falciparum.Timepoint: PCR-corrected adequate clinical and parasitological response (ACPR) at Day 29 (i.e., 28 days post-dose) in Parts A and B. | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess the key PK parameters of KAF156 and lumefantrine.Timepoint: PK assessments;To evaluate the safety and tolerability of KAF156/LUM-SDF.Timepoint: Standard safety/tolerability assessments: AE incidence and severity, liver and kidney function tests and electrocardiogram (ECG) abnormalities.;To further assess the effect of treatment with KAF156/LUM-SDF by assessing uncorrected ACPR and corrected ACPR at additional time points, as well asfever- and parasite clearance times.Timepoint: PCR-Uncorrected ACPR at Days 15, 29 and 43 (i.e., 14, 28 and 42 days postdose). PCR-corrected ACPR at Days 15 and 43 (i.e 14 and 42 days post-dose) Incidence rate of recrudescence and reinfection at Days 15, 29 and 43 Parasite and Fever Clearance Times (PCT and FCT). Proportion of patients with parasitaemia at 12, 24, and 48 hours after treatment. | — |
Countries
Burkina Faso, Gabon, Gambia, India, Kenya, Mali, Mozambique, Thailand, Uganda, Viet Nam
Contacts
Public ContactMurugananthan K
Novartis Healthcare Private Limited
Outcome results
None listed