Clinical trial NCT01616277: A Phase 1 Study To Evaluate The Safety And Tolerability Of PF-06252616 In Healthy Subjects
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of PF-06252616 In Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2012-06-11
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to determine if the study drug, PF-06252616 is safe and well tolerated when given to adult healthy volunteers.


Eligibility criteria: Inclusion Criteria:

* Single Dose Cohorts-Healthy male and/or female non-child bearing subjects between the ages of 18 and 55 years, inclusive.
* Repeat Dose Cohort-Healthy male and/or female non-child bearing subjects between the ages of 18 and less than 65 years, inclusive.

Exclusion Criteria:

* Presence or history of muscle disease (eg, polymyositis or rhabdomyolysis).
* Weight loss or gain of \>5% within 30 days of Screening, as reported by subject.
* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, immunologic, metabolic urologic, dermatologic, renal, allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) and any other major disease.

Primary outcomes:
measure: Incidence of treatment related Adverse Events.
timeFrame: Day 197
measure: Severity of treatment related Adverse Events.
timeFrame: Day 197
measure: Incidence of abnormal lab findings.
timeFrame: Day 197
measure: Magnitude of abnormal lab findings.
timeFrame: Day 197
measure: Abnormal and clinically relevant changes in Blood Pressure.
timeFrame: Day 197
measure: Abnormal and clinically relevant changes in Pulse Rate.
timeFrame: Day 197
measure: Abnormal and clinically relevant changes in Respiratory Rate.
timeFrame: Day 197
measure: Abnormal and clinically relevant changes in temperature.
timeFrame: Day 197
measure: Abnormal and clinically relevant changes in ECG parameters.
timeFrame: Day 197
Secondary outcomes:
measure: PF-06252616 concentration in serum as measured by a validated PK assay for Cmax (maximum concentration)
timeFrame: Through Day 197 post dosing
measure: Pharmacodynamic activity as measured by serum concentrations of GDF-8 (myostatin) as measured by a GDF-8 assay
timeFrame: Through Day 197 post dosing
measure: Incidence of development of anti-drug antibody (ADA) as measured by an ADA assay
timeFrame: Through Day 197 post dosing
measure: Pharmacologic activity as measured by the percent change in lean body mass as measured by DXA
timeFrame: Through Day 113 post dosing
measure: PF-06252616 concentration in serum as measured by a validated PK assay for Tmax (time to reach maximum concentration)
timeFrame: Through Day 197 post dosing
measure: PF-06252616 concentration in serum as measured by a validated PK assay for AUCinf (area under the curve serum concentration-time profile from time zero to infinity
timeFrame: Through Day 197 post dosing
measure: PF-06252616 concentration in serum as measured by a validated PK assay for AUClast (area under the curve serum concentration from time zero to the time of the last quantifiable concentration)
timeFrame: Through Day 197 post dosing
measure: PF-06252616 concentration in serum as measured by a validated PK assay for t1/2 (half-life time for the serum concentration to decrease by half).
timeFrame: Through Day 197 post dosing
measure: PF-06252616 concentration in serum as measured by a validated PK assay for AUCτ (area under the curve serum concentration by dose interval)
timeFrame: Through Day 197 post dosing
measure: PF-06252616 concentration in serum as measured by a validated PK assay for MRT (mean residence time)
timeFrame: Through Day 197 post dosing
measure: PF-06252616 concentration in serum as measured by a validated PK assay for CL (rate of clearance from serum)
timeFrame: Through Day 197 post dosing
measure: PF-06252616 concentration in serum as measured by a validated PK assay for CLss (rate of steady state clearance from serum in the repeat dose cohort)
timeFrame: Through Day 197 post dosing
measure: PF-06252616 concentration in serum as measured by a validated PK assay for Vz /F(volume of distribution is the theoretical volume which the total amount of drug would need to be uniformly distributed to produce the desired concentration of a drug.)
timeFrame: Through Day 197 post dosing
measure: PF-06252616 concentration in serum as measured by a validated PK assay for Vss(volume of distribution is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired concentration of a drug.
timeFrame: Through Day 197 post dosing
measure: Steady state volume of distribution is the apparent volume of distribution at steady-state.)
timeFrame: Through Day 197 post dosing
measure: PF-06252616 concentration in serum as measured by a validated PK assay for RAC (accumulation ratio for AUC)
timeFrame: Through Day 197 post dosing
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Pfizer Investigational Site
state: Connecticut
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Wojciechowski J, Purohit VS, Harnisch LO, Dua P, Tan B, Nicholas T. Population PK and PD Analysis of Domagrozumab in Pediatric Patients with Duchenne Muscular Dystrophy. Clin Pharmacol Ther. 2022 Dec;112(6):1291-1302. doi: 10.1002/cpt.2747. Epub 2022 Oct 4.