Efficacy, Safety, Tolerability and Pharmacokinetics of KAE609 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection
Study Details
Study Description
Brief Summary
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1 10 subjects with Plasmodium vivax malaria will receive 30 mg KAE609 once a day for three days |
Drug: KAE609
KAE609 was supplied as capsules for oral use.
|
| Experimental: Cohort 2 10 subjects with Plasmodium falciparum malaria will receive 30 mg KAE609 once a day for three days |
Drug: KAE609
KAE609 was supplied as capsules for oral use.
|
Outcome Measures
Primary Outcome Measures
- Parasite clearance time [From baseline to the time point when the blood parasite count is zero(up to a maximum of 5 days)]
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.
Secondary Outcome Measures
- Number of participants with adverse events [vital signs: Days 1 through 6; ECG: Days1, 2, 3; Labs: Days 2, 3, 5, study completion]
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.
- Area under the curve (AUC)0-24h on Day 1 and Day 3 [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
- The accumulation ratio (Racc) (=AUC0-24h, day3/AUC0-24h, day1) [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
- Maximum concentration (Cmax) on Day 1 and Day 3 [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
- Time to maximum concentration (Tmax) on Day 1 and Day 3 [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
- Half-life (T1/2) [Day 3]
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
- Clearance (CL/F ) [Day 3]
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
- The apparent volume of distribution during the terminal elimination phase following extravascular administration (Vz/F) [Day 3]
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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male and female patients aged 20 to 60 years
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Presence of mono-infection of P. falciparum or P. vivax
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Weight between 40 kg to 90 kg
Exclusion Criteria:
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Patients with signs and symptoms of severe/complicated malaria
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Mixed Plasmodium infection
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Presence of other serious or chronic clinical condition requiring hospitalization.
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Severe malnutrition
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Significant chronic medical conditions which in the opinion of the investigator preclude enrollment into the study
Other protocol-defined inclusion/exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Bangkok | Thailand | 10400 | |
| 2 | Novartis Investigative Site | Tak Province | Thailand | 63110 | |
| 3 | Novartis Investigative Site | Tak | Thailand | 63110 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CKAE609X2201