Efficacy, Safety, Tolerability and Pharmacokinetics of KAE609 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection

Study Overview
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Brief Summary
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This study will assess efficacy, safety , tolerability and PK in uncomplicated adult malaria patients with P. vivax or P. falciparum infection after 3 day dosing with KAE609 at 30 mg/day

Official Title
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A Proof-of-concept, Open Label, 3-day Repeated Dose Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of KAE609 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection

Conditions
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Malaria

Intervention / Treatment
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* Drug: KAE609


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients aged 20 to 60 years Presence of mono-infection of P. falciparum or P. vivax Weight between 40 kg to 90 kg Exclusion Criteria: Patients with signs and symptoms of severe/complicated malaria Mixed Plasmodium infection Presence of other serious or chronic clinical condition requiring hospitalization. Severe malnutrition Significant chronic medical conditions which in the opinion of the investigator preclude enrollment into the study Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>10 subjects with Plasmodium vivax malaria will receive 30 mg KAE609 once a day for three days | Drug: KAE609<br>* KAE609 was supplied as capsules for oral use.<br>|
| Experimental: Cohort 2<br>10 subjects with Plasmodium falciparum malaria will receive 30 mg KAE609 once a day for three days | Drug: KAE609<br>* KAE609 was supplied as capsules for oral use.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parasite clearance time | Calculated based on parasite count in blood. In thin film, use actual WBCs/µl, of blood to calculate parasite density by using the following formula: parasites/µl= #parasites× actual WBC/#WBCs counted. In thick film, assume that there are 250 RBCs per HPF, RBC count from 8 HPF equal 2000 RBC, Use actual RBCs/µl blood to calculate parasite density by using the following formula: parasites/µl= # of parasites in 8HPF/2000)× actual RBC. | From baseline to the time point when the blood parasite count is zero(up to a maximum of 5 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events | Number of participants with adverse events determined by Vital sign(body temperature, blood pressure and pulse rate): pre dose, 4, 8, 12, 16, 20, 24 hours post dose on Day 1: then 6, 12, 18, 24 hours post dose on each day during domiciles period until at least two consecutive normal temperature readings are obtained, then it will measure daily until Day 6. ECG: 3-4 hours post dose on day1; pre dose, 3-4 hours post dose on Day 2; pre dose, 3-4 hours post dose on Day 3 and study completion. Lab evaluation: Day 2, Day3 and Day5, study completion. | vital signs: Days 1 through 6; ECG: Days1, 2, 3; Labs: Days 2, 3, 5, study completion | 
| Area under the curve (AUC)0-24h on Day 1 and Day 3 | The parent drug in plasma samples will be analyzed. On Day 1: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. *The 24h sampling of first post dose should be taken before the second dose. On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose | Day 1 and Day 3 | 
| The accumulation ratio (Racc) (=AUC0-24h, day3/AUC0-24h, day1) | The parent drug in plasma samples will be analyzed. On Day 1: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. *The 24h sampling of first post dose should be taken before the second dose. On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose | Day 1 and Day 3 | 
| Maximum concentration (Cmax) on Day 1 and Day 3 | The parent drug in plasma samples will be analyzed. On Day 1: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. *The 24h sampling of first post dose should be taken before the second dose. On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose | Day 1 and Day 3 | 
| Time to maximum concentration (Tmax) on Day 1 and Day 3 | The parent drug in plasma samples will be analyzed. On Day 1: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. *The 24h sampling of first post dose should be taken before the second dose. On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose | Day 1 and Day 3 | 
| Half-life (T1/2) | The parent drug in plasma samples will be analyzed On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose | Day 3 | 
| Clearance (CL/F ) | The parent drug in plasma samples will be analyzed On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose | Day 3 | 
| The apparent volume of distribution during the terminal elimination phase following extravascular administration (Vz/F) | The parent drug in plasma samples will be analyzed. On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose | Day 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute malaria, KAE609