Trial Outcomes & Findings for A Study to Evaluate the Pharmacokinetics of Oral Formulations of MMV390048 Administered Fasted to Healthy Volunteers (NCT NCT02554799)

Results Overview

Maximum concentration (Cmax) of two MMV390048 prototype formulations administered in the fasted state

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

18 participants

Primary outcome timeframe

Up to 672 hours post-dose

Results posted on

2019-09-10

Participant Flow

Optional Cohort: The study design of this clinical trial allowed for an optional cohort to be enrolled. Ultimately, such optional cohort was not deemed required and therefore not conducted.

Participant milestones

Participant milestones
Measure	40 mg MMV390048 Form A Fasted 40 mg MMV390048 tablet formulation A fasted	40 mg MMV390048 Form B Fasted 40 mg MMV390048 tablet formulation B fasted
Overall Study STARTED	9	9
Overall Study COMPLETED	9	9
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Evaluate the Pharmacokinetics of Oral Formulations of MMV390048 Administered Fasted to Healthy Volunteers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	40 mg MMV390048 Form A Fasted n=9 Participants 40 mg MMV390048 tablet formulation A fasted	40 mg MMV390048 Form B Fasted n=9 Participants 40 mg MMV390048 tablet formulation B fasted	Total n=18 Participants Total of all reporting groups
Age, Continuous	29 years STANDARD_DEVIATION 10.37 • n=5 Participants	26 years STANDARD_DEVIATION 11.5 • n=7 Participants	28.5 years STANDARD_DEVIATION 10.65 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 672 hours post-dose

Maximum concentration (Cmax) of two MMV390048 prototype formulations administered in the fasted state

Outcome measures

Outcome measures
Measure	40 mg MMV390048 Form A Fasted n=9 Participants 40 mg MMV390048 tablet formulation A fasted	40 mg MMV390048 Form B Fasted n=9 Participants 40 mg MMV390048 tablet formulation B fasted
Cmax: Peak Plasma Concentration	277 ng/mL Standard Deviation 62.5	373.4444 ng/mL Standard Deviation 64.7825

PRIMARY outcome

Timeframe: Up to 672 hours post-dose

Time to reach maximum plasma concentration (Tmax) of two MMV390048 prototype formulations administered in the fasted state

Outcome measures

Outcome measures
Measure	40 mg MMV390048 Form A Fasted n=9 Participants 40 mg MMV390048 tablet formulation A fasted	40 mg MMV390048 Form B Fasted n=9 Participants 40 mg MMV390048 tablet formulation B fasted
Tmax: Time to Reach Peak Plasma Concentration	2.4 hours Standard Deviation 1.01	2.6 hours Standard Deviation 0.53

PRIMARY outcome

Timeframe: From Pre-dose to 672 hours post-dose

Area under the plasma concentration-time curve (AUC) of two MMV390048 prototype formulations administered in the fasted state

Outcome measures

Outcome measures
Measure	40 mg MMV390048 Form A Fasted n=9 Participants 40 mg MMV390048 tablet formulation A fasted	40 mg MMV390048 Form B Fasted n=9 Participants 40 mg MMV390048 tablet formulation B fasted
AUC: Area Under the Plasma Concentration-time Curve From Zero to Infinity	56991.64 h*ng/mL Standard Deviation 39197.535	63228.3 h*ng/mL Standard Deviation 29689.434

PRIMARY outcome

Timeframe: Up to 672 hours post-dose

Terminal elimination half-life (t1/2) of two MMV390048 prototype formulations administered in the fasted state

Outcome measures

Outcome measures
Measure	40 mg MMV390048 Form A Fasted n=9 Participants 40 mg MMV390048 tablet formulation A fasted	40 mg MMV390048 Form B Fasted n=9 Participants 40 mg MMV390048 tablet formulation B fasted
Terminal Elimination Half-life (t1/2)	192.0663 hours Standard Deviation 90.5336	160.3984 hours Standard Deviation 61.3228

PRIMARY outcome

Timeframe: Up to 672 hours post-dose

Terminal elimination rate constant (lambda z) of two MMV390048 prototype formulations administered in the fasted state

Outcome measures

Outcome measures
Measure	40 mg MMV390048 Form A Fasted n=9 Participants 40 mg MMV390048 tablet formulation A fasted	40 mg MMV390048 Form B Fasted n=9 Participants 40 mg MMV390048 tablet formulation B fasted
Terminal Elimination Rate Constant (Lambda z)	0.0041 1/hours Standard Deviation 0.0011	0.0051 1/hours Standard Deviation 0.0024

PRIMARY outcome

Timeframe: Up to 672 hours post-dose

Oral plasma clearance (CL/F) of two MMV390048 prototype formulations administered in the fasted state

Outcome measures

Outcome measures
Measure	40 mg MMV390048 Form A Fasted n=9 Participants 40 mg MMV390048 tablet formulation A fasted	40 mg MMV390048 Form B Fasted n=9 Participants 40 mg MMV390048 tablet formulation B fasted
Oral Plasma Clearance (CL/F)	0.8819 L/hours Standard Deviation 0.3473	0.7635 L/hours Standard Deviation 0.3658

PRIMARY outcome

Timeframe: Up to 672 hours post-dose

Apparent volume of distribution (Vz/F) of two MMV390048 prototype formulations administered in the fasted state

Outcome measures

Outcome measures
Measure	40 mg MMV390048 Form A Fasted n=9 Participants 40 mg MMV390048 tablet formulation A fasted	40 mg MMV390048 Form B Fasted n=9 Participants 40 mg MMV390048 tablet formulation B fasted
Apparent Volume of Distribution (Vz/F)	211.9523 Litres Standard Deviation 45.8906	155.3750 Litres Standard Deviation 49.9488

Adverse Events

40 mg MMV390048 Form A Fasted

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

40 mg MMV390048 Form B Fasted

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	40 mg MMV390048 Form A Fasted n=9 participants at risk 40 mg MMV390048 tablet formulation A fasted	40 mg MMV390048 Form B Fasted n=9 participants at risk 40 mg MMV390048 tablet formulation B fasted
Gastrointestinal disorders Constipation	0.00% 0/9 • Up to 672 hours post-dose (=study completion)	11.1% 1/9 • Number of events 1 • Up to 672 hours post-dose (=study completion)
Gastrointestinal disorders Dyspepsia	11.1% 1/9 • Number of events 1 • Up to 672 hours post-dose (=study completion)	0.00% 0/9 • Up to 672 hours post-dose (=study completion)
Infections and infestations Upper Respiratory Tract Infection	0.00% 0/9 • Up to 672 hours post-dose (=study completion)	11.1% 1/9 • Number of events 1 • Up to 672 hours post-dose (=study completion)
Infections and infestations Viral Upper Respiratory Tract Infection	22.2% 2/9 • Number of events 2 • Up to 672 hours post-dose (=study completion)	0.00% 0/9 • Up to 672 hours post-dose (=study completion)
Injury, poisoning and procedural complications Injury	0.00% 0/9 • Up to 672 hours post-dose (=study completion)	11.1% 1/9 • Number of events 1 • Up to 672 hours post-dose (=study completion)
Injury, poisoning and procedural complications Ligament Sprain	0.00% 0/9 • Up to 672 hours post-dose (=study completion)	11.1% 1/9 • Number of events 1 • Up to 672 hours post-dose (=study completion)
Nervous system disorders Headache	0.00% 0/9 • Up to 672 hours post-dose (=study completion)	22.2% 2/9 • Number of events 2 • Up to 672 hours post-dose (=study completion)
Respiratory, thoracic and mediastinal disorders Nasal Congestion	11.1% 1/9 • Number of events 1 • Up to 672 hours post-dose (=study completion)	0.00% 0/9 • Up to 672 hours post-dose (=study completion)
Skin and subcutaneous tissue disorders Rash	0.00% 0/9 • Up to 672 hours post-dose (=study completion)	11.1% 1/9 • Number of events 1 • Up to 672 hours post-dose (=study completion)

Additional Information

Dr Cristina Donini

Medicines for Malaria Venture

Phone: +41 22 555 0312

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Richmond Pharmacology Limited (RPL) shall not issue or submit any press release for publication without MMV's prior written approval. In recognition that RPL and the Site Principal Investigator have a responsibility to ensure that results of scientific interest arising from a Clinical Trial are appropriately published and disseminated, RPL may, upon MMV's written consent which will not be unreasonably withheld, publish Results of a clinical trial carried out under a Project Agreement.
Publication restrictions are in place

Restriction type: OTHER