A Study of the Safety, Tolerability, and Pharmacokinetics of SPR720 in Healthy Volunteers
- Conditions
- Healthy Volunteers
- Interventions
- Drug: Placebo for MADDrug: SPR720 for SADDrug: SPR720 for MADDrug: Placebo for SAD
- Registration Number
- NCT03796910
- Lead Sponsor
- Spero Therapeutics
- Brief Summary
The purpose of the study is to evaluate the safety, tolerability, and pharmacokinetics (PK) following single and multiple ascending dose administration of SPR720 administered orally in healthy volunteers.
- Detailed Description
This is a single-center, phase I, randomized, double-blind, placebo-controlled, first-in-man study. Up to 120 healthy volunteers may be enrolled in this 2-part, multi-cohort study. In both Part 1 and Part 2, sequential cohorts will be exposed to increasing doses of SPR720. Each cohort will enrol 8 subjects, randomized (3:1) to receive SPR720 (6 subjects) or placebo (2 subjects). Each subject will be assigned to only one cohort.
In Part 1 single ascending dose (SAD):
A single oral dose of SPR720 (n=6) or placebo (n=2) will be administered to 8 subjects at an initial dose level of 100 mg. Additional cohorts of 8 subjects will be enrolled to investigate increasing doses of SPR720 ranging from 250 mg to 3000 mg. All subjects will receive SPR720 (or placebo) by oral administration in the fasted state. One Part 1 cohort (the Food Effect Cohort) will receive an additional single dose of SPR720 (or placebo) in the fed state.
Part 2 multiple ascending dose (MAD):
SPR720 (or placebo) will be administered to approximately 3 planned dose cohorts of 8 subjects each. Subjects will receive SPR720 (or placebo) orally once daily for 7 (or 14) consecutive days starting with a planned initial dose of 500 mg. Additional cohorts of 8 subjects will be enrolled to investigate repeated daily doses of SPR720 ranging from 1000 mg to 1500 mg.
For both Part 1 and Part 2, a Safety Monitoring Group (SMG) will review cumulative safety and PK data from each cohort before proceeding to the next cohort/dose level. Doses to be evaluated in each subsequent cohort may be modified by the SMG based on review of safety and PK data from preceding cohorts. Part 2 will run concurrent with Part 1 and will be initiated following SMG review of safety and PK data for the corresponding Part 1 dose level cohort.
Part 1 will be conducted in up to 64 subjects (8 planned dose cohorts of 8 subjects each). Part 2 will be conducted in up to 24 subjects (3 planned dose cohorts of 8 subjects each); additional cohorts of 8 subjects each (up to 16 additional subjects) may be enrolled in either Part if further investigation of SPR720 is required.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 96
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Placebo for MAD Placebo for MAD 2 out of 8 subjects per cohort will be randomized to receive placebo SPR720 for SAD SPR720 for SAD 6 out of 8 subjects per cohort will be randomized to receive SPR720 SPR720 for MAD SPR720 for MAD 6 out of 8 subjects per cohort will be randomized to receive SPR720 Placebo for SAD Placebo for SAD 2 out of 8 subjects per cohort will be randomized to receive placebo
- Primary Outcome Measures
Name Time Method Treatment emergent adverse events assessments after single and multiple dose administration at baseline and repeatedly until study completion [Safety and Tolerability] Day 1 through last follow-up visit (5-7 days after last dose) Incidence and severity of AEs
- Secondary Outcome Measures
Name Time Method Assessment of Pharmacokinetic Parameter (plasma): Cmax measurement From Day 1 pre-dose to 48 hours post last dose Maximum concentration of study drug in plasma
Assessment of Pharmacokinetic Parameter (plasma): CmaxSS measurement From Day 1 pre-dose to 48 hours post last dose Maximum concentration of study drug in plasma at steady state
Assessment of Pharmacokinetic Parameter (plasma): CminSS From Day 1 pre-dose to 48 hours post last dose Lowest concentration of study drug in a dosing interval in plasma
Assessment of Pharmacokinetic Parameter (plasma): Ctrough From Day 1 pre-dose to 48 hours post last dose Concentration of study drug at the end of the dosing interval in plasma
Assessment of Pharmacokinetic Parameter (plasma): CavSS From Day 1 pre-dose to 48 hours post last dose Average concentration of study drug in plasma during a dosing interval
Assessment of Pharmacokinetic Parameter (plasma): Tmax From Day 1 pre-dose to 48 hours post last dose The time to maximum observed concentration of study drug in plasma
Assessment of Pharmacokinetic Parameter (plasma): kel From Day 1 pre-dose to 48 hours post last dose Elimination rate constant of study drug in plasma
Assessment of Pharmacokinetic Parameter (plasma): t1/2 From Day 1 pre-dose to 48 hours post last dose Terminal elimination half-life of study drug in plasma
Assessment of Pharmacokinetic Parameter (plasma): AUC0-24 From Day 1 pre-dose to 48 hours post last dose Area under the concentration-time curve (AUC) of study drug in plasma from 0 to 24 hours post dose (dose escalation)
Assessment of Pharmacokinetic Parameter (plasma): AUC0-tau From Day 1 pre-dose to 48 hours post last dose Area under the concentration-time curve (AUC) from 0 to tau, where tau is the dosing interval (multiple dose only) of study drug in plasma
Assessment of Parameter (plasma): AUC0-t From Day 1 pre-dose to 48 hours post last dose Area under the concentration-time curve (AUC) of study drug in plasma from the time of dosing to the time of the last measurable concentration
Assessment of Pharmacokinetic Parameter (plasma): AUC0-inf From Day 1 pre-dose to 48 hours post last dose AUC extrapolated to infinity of study drug in plasma
Assessment of Parameter (plasma): AUC%extrapolated From Day 1 pre-dose to 48 hours post last dose Residual area of study drug in plasma
Assessment of Pharmacokinetic Parameter (plasma): Degree of fluctuation From Day 1 pre-dose to 48 hours post last dose (Cmax-Cmin)/Cavss of study drug in plasma
Assessment of Pharmacokinetic Parameter (plasma): Swing From Day 1 pre-dose to 48 hours post last dose (Cmaxss-Cminss)/Cminss of study drug in plasma
Assessment of Pharmacokinetic Parameter (urine): SPR719 From Day 1 pre-dose to 24 hours post last dose amount of SPR719 excreted in urine
Trial Locations
- Locations (1)
Simbec Research, Ltd.
🇬🇧Merthyr Tydfil,, Mid Glamorgan, United Kingdom