Trial Outcomes & Findings for A Study to Find the Minimum Inhibitory Concentration of KAE609 in Adult Male Patients With P. Falciparum Monoinfection (NCT NCT01836458)

Last Updated: 2016-10-31

Results Overview

To observe the exposure-response (PK/PD) relationship for a single dose of KAE609. The key parameter is MIC, defined as the concentration at which the relative rate of change in parasitemia is equal to zero. Approximation of MIC will assist in identifying the optimal dose of KAE609, which will be one component of a future combination antimalarial. MIC could not be determined due to small sample size no data was collected from any participants.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

25 participants

Primary outcome timeframe

Up to Day 8 after a single dose of KAE609

Results posted on

2016-10-31

Participant Flow

Participant milestones

Participant milestones
Measure	Dose 1: 30 mg Single dose of KAE609 30 mg	Dose 2: 20 mg Single dose of KAE609 20 mg	Dose 3: 10 mg Single dose of KAE609 10 mg	Dose 4: 15 mg Single dose of KAE609 15 mg
Overall Study STARTED	7	4	7	7
Overall Study COMPLETED	4	2	2	1
Overall Study NOT COMPLETED	3	2	5	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose 1: 30 mg Single dose of KAE609 30 mg	Dose 2: 20 mg Single dose of KAE609 20 mg	Dose 3: 10 mg Single dose of KAE609 10 mg	Dose 4: 15 mg Single dose of KAE609 15 mg
Overall Study Unsatisfactory therapeutic effect	3	2	5	6

Baseline Characteristics

A Study to Find the Minimum Inhibitory Concentration of KAE609 in Adult Male Patients With P. Falciparum Monoinfection

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose 1: 30 mg n=7 Participants Single dose of KAE609 30 mg	Dose 2: 20 mg n=4 Participants Single dose of KAE609 20 mg	Dose 3: 10 mg n=7 Participants Single dose of KAE609 10 mg	Dose 4: 15 mg n=7 Participants Single dose of KAE609 15 mg	Total n=25 Participants Total of all reporting groups
Age, Continuous	32.7 years STANDARD_DEVIATION 11.84 • n=5 Participants	32.8 years STANDARD_DEVIATION 7.93 • n=7 Participants	30.6 years STANDARD_DEVIATION 8.24 • n=5 Participants	34.7 years STANDARD_DEVIATION 8.79 • n=4 Participants	32.7 years STANDARD_DEVIATION 9.04 • n=21 Participants
Sex/Gender, Customized MALE	7 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants	7 participants n=4 Participants	25 participants n=21 Participants

PRIMARY outcome

Timeframe: Up to Day 8 after a single dose of KAE609

Population: The primary Outcome Measure (OM) could not be determined due to small sample size no data was collected from any participants.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 54, 60, 66, 72 hours post dose of KAE609

Population: Pharmacodynamic Analysis Set includes all enrolled patients

Parasite clearance time will be estimated using thick/thin blood films.

Outcome measures

Outcome measures
Measure	Dose 1: 30 mg n=7 Participants Single dose of KAE609 30 mg	Dose 2: 20 mg n=4 Participants Single dose of KAE609 20 mg	Dose 3: 10 mg n=7 Participants Single dose of KAE609 10 mg	Dose 4: 15 mg n=7 Participants Single dose of KAE609 15 mg
Median Time to Parasite Clearance	24.00 hours Interval 12.0 to 48.0	63.00 hours Interval 36.02 to 72.0	54.00 hours Interval 36.05 to Only 4 of 7 patients reached time to parasite clearance; therefore, it was not possible to calculate the upper limit of the 95% confidence interval.	60.00 hours Interval 36.0 to 72.0

SECONDARY outcome

Timeframe: Day 1 to Day 5

Population: Pharmacodynamic Analysis Set includes all enrolled patients

Fever is monitored on participants every 4 hours for the first 24 hours, then every 6 hours until negative reading obtained.

Outcome measures

Outcome measures
Measure	Dose 1: 30 mg n=7 Participants Single dose of KAE609 30 mg	Dose 2: 20 mg n=4 Participants Single dose of KAE609 20 mg	Dose 3: 10 mg n=7 Participants Single dose of KAE609 10 mg	Dose 4: 15 mg n=7 Participants Single dose of KAE609 15 mg
Median Time to Fever Clearance	9.83 hours Interval 0.83 to 11.92	12.38 hours Interval 3.83 to 29.83	15.75 hours Interval 0.75 to 15.83	11.83 hours Interval 4.83 to 35.83

SECONDARY outcome

Timeframe: Day 28, Day 35 & Day 42

Population: Pharmacodynamic Analysis Set includes all enrolled patients.

PCR-corrected cure rate after a single dose of KAE609 by Day 28, Day 35 \& Day 42. PCR-corrected cure rate accounts for failures due to reappearance of parasites that were present in the blood before treatment (i.e. recrudescent infection) but not for failures due to a post-treatment inoculation (i.e. new infection).

Outcome measures

Outcome measures
Measure	Dose 1: 30 mg n=7 Participants Single dose of KAE609 30 mg	Dose 2: 20 mg n=4 Participants Single dose of KAE609 20 mg	Dose 3: 10 mg n=7 Participants Single dose of KAE609 10 mg	Dose 4: 15 mg n=7 Participants Single dose of KAE609 15 mg
Percentage of Patients PCR-corrected Cure Rate by Day 28, Day 35 & Day 42 Day 28	57.1 Percentage of Patients	50.0 Percentage of Patients	28.6 Percentage of Patients	14.3 Percentage of Patients
Percentage of Patients PCR-corrected Cure Rate by Day 28, Day 35 & Day 42 Day 35	57.1 Percentage of Patients	50.0 Percentage of Patients	28.6 Percentage of Patients	14.3 Percentage of Patients
Percentage of Patients PCR-corrected Cure Rate by Day 28, Day 35 & Day 42 Day 42	57.1 Percentage of Patients	50.0 Percentage of Patients	28.6 Percentage of Patients	14.3 Percentage of Patients

Adverse Events

Dose 1: 30mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Dose 2: 20mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Dose 3: 10mg

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Dose 4: 15mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Dose 1: 30mg n=7 participants at risk Single dose of KAE609 30 mg	Dose 2: 20mg n=4 participants at risk Single dose of KAE609 20 mg	Dose 3: 10mg n=7 participants at risk Single dose of KAE609 10 mg	Dose 4: 15mg n=7 participants at risk Single dose of KAE609 15 mg
Blood and lymphatic system disorders Anaemia	0.00% 0/7	0.00% 0/4	14.3% 1/7	0.00% 0/7
Gastrointestinal disorders Abdominal pain upper	0.00% 0/7	0.00% 0/4	14.3% 1/7	0.00% 0/7
Gastrointestinal disorders Abnormal faeces	0.00% 0/7	25.0% 1/4	0.00% 0/7	0.00% 0/7
Gastrointestinal disorders Diarrhoea	0.00% 0/7	0.00% 0/4	0.00% 0/7	14.3% 1/7
Gastrointestinal disorders Nausea	14.3% 1/7	0.00% 0/4	14.3% 1/7	0.00% 0/7
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/7	25.0% 1/4	42.9% 3/7	14.3% 1/7
Investigations Alanine aminotransferase increased	14.3% 1/7	0.00% 0/4	0.00% 0/7	0.00% 0/7
Investigations Blood alkaline phosphatase increased	14.3% 1/7	50.0% 2/4	42.9% 3/7	57.1% 4/7
Musculoskeletal and connective tissue disorders Myalgia	14.3% 1/7	0.00% 0/4	0.00% 0/7	0.00% 0/7
Nervous system disorders Headache	14.3% 1/7	25.0% 1/4	0.00% 0/7	0.00% 0/7
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/7	25.0% 1/4	0.00% 0/7	0.00% 0/7
Skin and subcutaneous tissue disorders Rash vesicular	0.00% 0/7	0.00% 0/4	0.00% 0/7	14.3% 1/7
Vascular disorders Hypertensive crisis	14.3% 1/7	0.00% 0/4	0.00% 0/7	0.00% 0/7

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER