Trial Outcomes & Findings for Malaria: Relative Bioavailability and Food Effect of DSM265 (NCT NCT03637517)

NCT ID: NCT03637517

Last Updated: 2020-03-11

Results Overview

Maximum observed DSM265 plasma concentration

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 42 participants
• Primary outcome timeframe: 21 days
• Results posted on: 2020-03-11

Participant Flow

Clinical Pharmacology phase 1 unit.

30 day screening period.

Participant milestones

Measure	DSM265 25% SDD, 400 mg Fasted Spray dried dispersion (SDD) formulation, powder containing 25% DSM265 as free base DSM265 25% SDD, 400 mg fasted: Reference formulation used in early clinical trials.	DSM265-TPGS 34% SDD, 400 mg Fasted Spray dried dispersion (SDD) formulation, powder containing 34.25% DSM265-TPGS (tocopheryl polyethylene glycol succinate) DSM265-TPGS 34% SDD, 400 mg fasted: New formulation allowing smaller volumes of dissolution in a common vehicle (water), administered to subjects in a fasted state.	DSM265-TPGS 34% SDD, 400 mg Fed Spray dried dispersion (SDD) formulation, powder containing 34.25% DSM265-TPGS (tocopheryl polyethylene glycol succinate) DSM265-TPGS 34% SDD, 400 mg fed: New formulation allowing smaller volumes of dissolution in a common vehicle (water), administered to subjects in a fed state.
Overall Study STARTED	14	14	14
Overall Study COMPLETED	14	14	14
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Malaria: Relative Bioavailability and Food Effect of DSM265

Baseline characteristics by cohort

Measure	DSM265 25% SDD, 400 mg Fasted n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 25% DSM265 as free base DSM265 25% SDD, 400 mg fasted: Reference formulation used in early clinical trials.	DSM265-TPGS 34% SDD, 400 mg Fasted n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 34.25% DSM265-TPGS (tocopheryl polyethylene glycol succinate) DSM265-TPGS 34% SDD, 400 mg fasted: New formulation allowing smaller volumes of dissolution in a common vehicle (water), administered to subjects in a fasted state.	DSM265-TPGS 34% SDD, 400 mg Fed n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 34.25% DSM265-TPGS (tocopheryl polyethylene glycol succinate) DSM265-TPGS 34% SDD, 400 mg fed: New formulation allowing smaller volumes of dissolution in a common vehicle (water), administered to subjects in a fed state.	Total n=42 Participants Total of all reporting groups
Age, Continuous	37.9 years STANDARD_DEVIATION 10.78 • n=5 Participants	36.1 years STANDARD_DEVIATION 9.23 • n=7 Participants	38.6 years STANDARD_DEVIATION 10.58 • n=5 Participants	37.6 years STANDARD_DEVIATION 10.02 • n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	9 Participants n=4 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants	33 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants	14 Participants n=7 Participants	12 Participants n=5 Participants	39 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 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	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	8 Participants n=7 Participants	3 Participants n=5 Participants	17 Participants n=4 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants	22 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	14 participants n=5 Participants	14 participants n=7 Participants	14 participants n=5 Participants	42 participants n=4 Participants

PRIMARY outcome

Timeframe: 21 days

Maximum observed DSM265 plasma concentration

Outcome measures

Measure	DSM265 25% SDD, 400 mg Fasted n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 25% DSM265 as free base DSM265 25% SDD, 400 mg fasted: Reference formulation used in early clinical trials.	DSM265-TPGS 34% SDD, 400 mg Fasted n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 34.25% DSM265-TPGS (tocopheryl polyethylene glycol succinate) DSM265-TPGS 34% SDD, 400 mg fasted: New formulation allowing smaller volumes of dissolution in a common vehicle (water), administered to subjects in a fasted state.	DSM265-TPGS 34% SDD, 400 mg Fed n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 34.25% DSM265-TPGS (tocopheryl polyethylene glycol succinate) DSM265-TPGS 34% SDD, 400 mg fed: New formulation allowing smaller volumes of dissolution in a common vehicle (water), administered to subjects in a fed state.
Cmax	15300 NG/ML Geometric Coefficient of Variation 27	14200 NG/ML Geometric Coefficient of Variation 28	11200 NG/ML Geometric Coefficient of Variation 27

PRIMARY outcome

Timeframe: 168 hours

Area under the plasma concentration-time curve from time 0 to 168 hours (AUC168)

Outcome measures

Measure	DSM265 25% SDD, 400 mg Fasted n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 25% DSM265 as free base DSM265 25% SDD, 400 mg fasted: Reference formulation used in early clinical trials.	DSM265-TPGS 34% SDD, 400 mg Fasted n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 34.25% DSM265-TPGS (tocopheryl polyethylene glycol succinate) DSM265-TPGS 34% SDD, 400 mg fasted: New formulation allowing smaller volumes of dissolution in a common vehicle (water), administered to subjects in a fasted state.	DSM265-TPGS 34% SDD, 400 mg Fed n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 34.25% DSM265-TPGS (tocopheryl polyethylene glycol succinate) DSM265-TPGS 34% SDD, 400 mg fed: New formulation allowing smaller volumes of dissolution in a common vehicle (water), administered to subjects in a fed state.
AUC168	1100000 NG*H/ML Geometric Coefficient of Variation 14	987000 NG*H/ML Geometric Coefficient of Variation 17	1160000 NG*H/ML Geometric Coefficient of Variation 22

PRIMARY outcome

Timeframe: 21 days

AUC from time 0 until the last measurable concentration (AUCt),

Outcome measures

Measure	DSM265 25% SDD, 400 mg Fasted n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 25% DSM265 as free base DSM265 25% SDD, 400 mg fasted: Reference formulation used in early clinical trials.	DSM265-TPGS 34% SDD, 400 mg Fasted n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 34.25% DSM265-TPGS (tocopheryl polyethylene glycol succinate) DSM265-TPGS 34% SDD, 400 mg fasted: New formulation allowing smaller volumes of dissolution in a common vehicle (water), administered to subjects in a fasted state.	DSM265-TPGS 34% SDD, 400 mg Fed n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 34.25% DSM265-TPGS (tocopheryl polyethylene glycol succinate) DSM265-TPGS 34% SDD, 400 mg fed: New formulation allowing smaller volumes of dissolution in a common vehicle (water), administered to subjects in a fed state.
AUCt	1750000 NG*H/ML Geometric Coefficient of Variation 20	1570000 NG*H/ML Geometric Coefficient of Variation 19	1840000 NG*H/ML Geometric Coefficient of Variation 20

PRIMARY outcome

Timeframe: 21 days

Time to Cmax.

Outcome measures

Measure	DSM265 25% SDD, 400 mg Fasted n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 25% DSM265 as free base DSM265 25% SDD, 400 mg fasted: Reference formulation used in early clinical trials.	DSM265-TPGS 34% SDD, 400 mg Fasted n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 34.25% DSM265-TPGS (tocopheryl polyethylene glycol succinate) DSM265-TPGS 34% SDD, 400 mg fasted: New formulation allowing smaller volumes of dissolution in a common vehicle (water), administered to subjects in a fasted state.	DSM265-TPGS 34% SDD, 400 mg Fed n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 34.25% DSM265-TPGS (tocopheryl polyethylene glycol succinate) DSM265-TPGS 34% SDD, 400 mg fed: New formulation allowing smaller volumes of dissolution in a common vehicle (water), administered to subjects in a fed state.
Tmax	2.4 Hours Standard Deviation 1.4	2.1 Hours Standard Deviation 0.9	11.4 Hours Standard Deviation 8.4

PRIMARY outcome

Timeframe: 21 days

Apparent terminal phase elimination rate constant

Outcome measures

Measure	DSM265 25% SDD, 400 mg Fasted n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 25% DSM265 as free base DSM265 25% SDD, 400 mg fasted: Reference formulation used in early clinical trials.	DSM265-TPGS 34% SDD, 400 mg Fasted n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 34.25% DSM265-TPGS (tocopheryl polyethylene glycol succinate) DSM265-TPGS 34% SDD, 400 mg fasted: New formulation allowing smaller volumes of dissolution in a common vehicle (water), administered to subjects in a fasted state.	DSM265-TPGS 34% SDD, 400 mg Fed n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 34.25% DSM265-TPGS (tocopheryl polyethylene glycol succinate) DSM265-TPGS 34% SDD, 400 mg fed: New formulation allowing smaller volumes of dissolution in a common vehicle (water), administered to subjects in a fed state.
β	0.00556 1/H Standard Deviation 0.00189	0.00531 1/H Standard Deviation 0.00154	0.00595 1/H Standard Deviation 0.00231

PRIMARY outcome

Timeframe: 7 days

Plasma concentration at 168 hours

Outcome measures

Measure	DSM265 25% SDD, 400 mg Fasted n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 25% DSM265 as free base DSM265 25% SDD, 400 mg fasted: Reference formulation used in early clinical trials.	DSM265-TPGS 34% SDD, 400 mg Fasted n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 34.25% DSM265-TPGS (tocopheryl polyethylene glycol succinate) DSM265-TPGS 34% SDD, 400 mg fasted: New formulation allowing smaller volumes of dissolution in a common vehicle (water), administered to subjects in a fasted state.	DSM265-TPGS 34% SDD, 400 mg Fed n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 34.25% DSM265-TPGS (tocopheryl polyethylene glycol succinate) DSM265-TPGS 34% SDD, 400 mg fed: New formulation allowing smaller volumes of dissolution in a common vehicle (water), administered to subjects in a fed state.
C168	4090 NG/ML Geometric Coefficient of Variation 25	3540 NG/ML Geometric Coefficient of Variation 25	4200 NG/ML Geometric Coefficient of Variation 24

SECONDARY outcome

Timeframe: 21 days

AUC from time 0 to infinity (AUCinf)

Outcome measures

Measure	DSM265 25% SDD, 400 mg Fasted n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 25% DSM265 as free base DSM265 25% SDD, 400 mg fasted: Reference formulation used in early clinical trials.	DSM265-TPGS 34% SDD, 400 mg Fasted n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 34.25% DSM265-TPGS (tocopheryl polyethylene glycol succinate) DSM265-TPGS 34% SDD, 400 mg fasted: New formulation allowing smaller volumes of dissolution in a common vehicle (water), administered to subjects in a fasted state.	DSM265-TPGS 34% SDD, 400 mg Fed n=14 Participants Spray dried dispersion (SDD) formulation, powder containing 34.25% DSM265-TPGS (tocopheryl polyethylene glycol succinate) DSM265-TPGS 34% SDD, 400 mg fed: New formulation allowing smaller volumes of dissolution in a common vehicle (water), administered to subjects in a fed state.
AUCinf	1960000 NG*H/ML Geometric Coefficient of Variation 29	1760000 NG*H/ML Geometric Coefficient of Variation 26	2040000 NG*H/ML Geometric Coefficient of Variation 23

Adverse Events

DSM265 25% SDD, 400 mg Fasted

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

DSM265-TPGS 34% SDD, 400 mg Fasted

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

DSM265-TPGS 34% SDD, 400 mg Fed

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Stephan Chalon, MD

Medicines for Malaria Venture

Phone: +41 22 555 0369

Email: chalons@mmv.org

Results disclosure agreements

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

Restriction type: LTE60