A Two-part, Randomized, Double-blind, Placebo-controlled, First-In-Human, Phase I Study of the Safety, Tolerability, and Pharmacokinetics of SPR720 Following Administration of Single and Multiple Ascending Oral Doses in Healthy Volunteers
Overview
- Phase
- Phase 1
- Intervention
- SPR720 for SAD
- Conditions
- Healthy Volunteers
- Sponsor
- Spero Therapeutics
- Enrollment
- 96
- Locations
- 1
- Primary Endpoint
- Treatment emergent adverse events assessments after single and multiple dose administration at baseline and repeatedly until study completion [Safety and Tolerability]
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
SPR720 for SAD
6 out of 8 subjects per cohort will be randomized to receive SPR720
Intervention: SPR720 for SAD
Placebo for SAD
2 out of 8 subjects per cohort will be randomized to receive placebo
Intervention: Placebo for SAD
SPR720 for MAD
6 out of 8 subjects per cohort will be randomized to receive SPR720
Intervention: SPR720 for MAD
Placebo for MAD
2 out of 8 subjects per cohort will be randomized to receive placebo
Intervention: Placebo for MAD
Outcomes
Primary Outcomes
Treatment emergent adverse events assessments after single and multiple dose administration at baseline and repeatedly until study completion [Safety and Tolerability]
Time Frame: Day 1 through last follow-up visit (5-7 days after last dose)
Incidence and severity of AEs
Secondary Outcomes
- Assessment of Pharmacokinetic Parameter (plasma): Cmax measurement(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): CmaxSS measurement(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): CminSS(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): Ctrough(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): CavSS(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): Tmax(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): kel(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): t1/2(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): AUC0-24(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): AUC0-tau(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Parameter (plasma): AUC0-t(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): AUC0-inf(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Parameter (plasma): AUC%extrapolated(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): Degree of fluctuation(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): Swing(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (urine): SPR719(From Day 1 pre-dose to 24 hours post last dose)