A Study to Assess Efficacy, Safety of KAE609 in Adult Patients With Acute Malaria Mono-infection
Study Details
Study Description
Brief Summary
This study will assess efficacy, safety , tolerability and PK in uncomplicated adult malaria patients with acute P. falciparum infection after single dose with KAE609 at 75 mg, 150mg, 225mg and 300mg/day
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
the study is comprised of 4 sequential cohorts, in total there will be up to 48 patients enrolled in the study.
cohort 1: 6-12 patients receive 75mg single dose. cohort 2: 6-12 patients receive 150mg single dose. cohort 3: 6-12 patients receive 225mg single dose. cohort 4: 6-12 patients receive 300mg single dose. After approximately every 6 patients in any cohort have been treated with a given dose and complete the first 15 days, a safety and tolerability data review will be conducted by a Data Monitoring Committee(DMC). Consensus agreement of DMC is required to either escalate to the next dose level or expand a given cohort with an additional 6 patients in order to obtain more safety data.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1 6-12 subjects with Plasmodium falciparum malaria will receive 75 mg KAE609 as a single dose |
Drug: KAE609
KAE609 75mg single dose
|
| Experimental: Cohort 2 6-12 subjects with Plasmodium falciparum malaria will receive 150 mg KAE609 as a single dose |
Drug: KAE609
KAE609 150mg single dose
|
| Experimental: Cohort 3 6 to 12 subjects with Plasmodium falciparum malaria will receive 225 mg KAE609 as a single dose |
Drug: KAE609
KAE609 225mg single dose
|
| Experimental: Cohort4 6- 12 subjects with Plasmodium falciparum malaria will receive 300 mg KAE609 as a single dose |
Drug: KAE609
KAE609 300mg single dose
|
Outcome Measures
Primary Outcome Measures
- 28-day Cure Rate [Day 28]
28-day cure rate was measured by the endpoint of complete cure without recrudescence before Day 29. The primary variable of 28-day cure rate was defined as the proportion of patients with clearance of asexual parasitemia (by blood film) by day 6 of the study, and without subsequent recrudescence (by blood film).
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male and female patients aged 20 to 60 years
-
Presence of mono-infection of P. falciparum
-
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Ratchabari | Thailand | 70180 | |
| 2 | Novartis Investigative Site | Srisaket | Thailand | 33140 | |
| 3 | Novartis Investigative Site | Tak | Thailand | 63140 | |
| 4 | Novartis Investigative Site | Hanoi | Vietnam | 10000 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CKAE609X2202
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Total - Cohort 1 |
|---|---|
| Arm/Group Description | Cohort 1 6-12 subjects with Plasmodium falciparum malaria will receive 75 mg KAE609 as a single dose |
| Period Title: Overall Study | |
| STARTED | 11 |
| COMPLETED | 6 |
| NOT COMPLETED | 5 |
Baseline Characteristics
| Arm/Group Title | Total - Cohort 1 |
|---|---|
| Arm/Group Description | Cohort 1 6-12 subjects with Plasmodium falciparum malaria will receive 75 mg KAE609 as a single dose |
| Overall Participants | 11 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
31.6
(7.50)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
0
0%
|
| Male |
11
100%
|
Outcome Measures
| Title | 28-day Cure Rate |
|---|---|
| Description | 28-day cure rate was measured by the endpoint of complete cure without recrudescence before Day 29. The primary variable of 28-day cure rate was defined as the proportion of patients with clearance of asexual parasitemia (by blood film) by day 6 of the study, and without subsequent recrudescence (by blood film). |
| Time Frame | Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PharmacoDynamic (PD) Analysis Set - All the 11 patients were included in PD analysis set. |
| Arm/Group Title | Total - Cohort 1 |
|---|---|
| Arm/Group Description | Cohort 1 6-12 subjects with Plasmodium falciparum malaria will receive 75 mg KAE609 as a single dose |
| Measure Participants | 11 |
| Number [Percentage of participants] |
63.67
578.8%
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Total - Cohort 1 | |
| Arm/Group Description | Cohort 1 6-12 subjects with Plasmodium falciparum malaria will receive 75 mg KAE609 as a single dose | |
All Cause Mortality |
||
| Total - Cohort 1 | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Total - Cohort 1 | ||
| Affected / at Risk (%) | # Events | |
| Total | 3/11 (27.3%) | |
| Hepatobiliary disorders | ||
| Jaundice | 1/11 (9.1%) | |
| Investigations | ||
| Alanine aminotransferase increased | 2/11 (18.2%) | |
| Aspartate aminotransferase increased | 1/11 (9.1%) | |
Other (Not Including Serious) Adverse Events |
||
| Total - Cohort 1 | ||
| Affected / at Risk (%) | # Events | |
| Total | 8/11 (72.7%) | |
| Blood and lymphatic system disorders | ||
| Thrombocytopenia | 1/11 (9.1%) | |
| Cardiac disorders | ||
| Bradycardia | 1/11 (9.1%) | |
| Sinus bradycardia | 1/11 (9.1%) | |
| Gastrointestinal disorders | ||
| Abdominal discomfort | 1/11 (9.1%) | |
| Dyspepsia | 1/11 (9.1%) | |
| Nausea | 3/11 (27.3%) | |
| Vomiting | 1/11 (9.1%) | |
| General disorders | ||
| Fatigue | 2/11 (18.2%) | |
| Pyrexia | 1/11 (9.1%) | |
| Infections and infestations | ||
| Upper respiratory tract infection | 1/11 (9.1%) | |
| Urinary tract infection | 1/11 (9.1%) | |
| Investigations | ||
| Alanine aminotransferase increased | 5/11 (45.5%) | |
| Aspartate aminotransferase increased | 4/11 (36.4%) | |
| Blood alkaline phosphatase increased | 2/11 (18.2%) | |
| Blood pressure systolic increased | 1/11 (9.1%) | |
| Electrocardiogram QT prolonged | 1/11 (9.1%) | |
| Platelet count decreased | 7/11 (63.6%) | |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 1/11 (9.1%) | |
| Hypokalaemia | 1/11 (9.1%) | |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 4/11 (36.4%) | |
| Nervous system disorders | ||
| Dizziness | 2/11 (18.2%) | |
| Headache | 3/11 (27.3%) | |
| Psychiatric disorders | ||
| Insomnia | 1/11 (9.1%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 2/11 (18.2%) | |
| Skin and subcutaneous tissue disorders | ||
| Hyperhidrosis | 1/11 (9.1%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
- CKAE609X2202