A Study To Assess The Safety, Tolerability, And Pharmacokinetics (PK) Of Multiple Doses Of PF-06865571 In Healthy, Including Overweight And Obese, Adult Subjects

A Phase 1, Randomized, Double-blind, Placebo-controlled Study To Assess The Safety, Tolerability, And Pharmacokinetics Of Multiple Escalating Oral Doses Of PF-06865571 In Healthy, Including Overweight And Obese, Adult Subjects

This will be an investigator- and subject-blinded (sponsor open), randomized, placebo controlled, sequential, ascending, multiple oral dose study, with 5 planned cohorts (optional sixth and seventh cohorts). A total of approximately 50 (if 5 cohorts), 60 (if 6 cohorts), and up to 70 (if 7 cohorts) subjects will be randomized in this study. Subjects in each cohort will be randomized to receive PF-06865571 or matching placebo with approximately 10 subjects dosed in each cohort.

For a given subject in any cohort, the total study duration from screening to follow-up phone call will be between approximately 7 to 11 weeks.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Placebo; Drug: PF-06865571

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, B-1070
    • Pfizer Clinical Research Unit
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Pfizer New Haven Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy males and female of non-childbearing potential;
• Age of 18-55, inclusive;
• Body Mass Index 22.5 to 35.4 kg/m2, inclusive;
• Body weight greater than 50 kg;
• Not on any prescription or non-prescription drugs within 7 days or 5 half-lives prior to first dose.

Exclusion Criteria:

• Evidence of history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergises, but excluding untreated, asymptomatic, seasonal allergies at time of dosing);
• Subjects with fasting LDL-C level >190 mg/dL following an overnight fast of at least 10 hours, at the Screening visit, confirmed by a single repeat, if deemed necessary.
• Subjects with fasting TG level >400 mg/dL following an overnight fast of at least 10 hours, at the Screening visit, confirmed by a single repeat, if deemed necessary.
• Any condition possibly affecting drug absorption (eg, gastrectomy).
• A positive urine drug test.
• History of regular alcohol consumption exceeding 7 drinks/week for female subjects or 14 drinks/week for male subjects (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 6 months before screening.
• Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of investigational product (whichever is longer).
• Use of tobacco- or nicotine-containing products in excess of the equivalent of 5 cigarettes per day or 2 chews of tobacco per day.
• Pregnant female subjects; breastfeeding female subjects; male subjects with partners currently pregnant; fertile male subjects who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product.
• Unwilling or unable to comply with the criteria in the Lifestyle Requirements section of this protocol.
• Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: DOUBLE

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 1_90mg and Matching Placebo	Drug: Placebo; Matching Placebo for PF-06865571 for each cohort.; Drug: PF-06865571; Multiple ascending dose of PF-06865571 as extemporaneously prepared suspension for 14 consecutive days with total daily dose of 90mg, 300mg, 900mg, 1800mg, 3000mg and TBD.
EXPERIMENTAL: Cohort 2_300mg and Matching Placebo	Drug: Placebo; Matching Placebo for PF-06865571 for each cohort.; Drug: PF-06865571; Multiple ascending dose of PF-06865571 as extemporaneously prepared suspension for 14 consecutive days with total daily dose of 90mg, 300mg, 900mg, 1800mg, 3000mg and TBD.
EXPERIMENTAL: Cohort 3_900mg and Matching Placebo	Drug: Placebo; Matching Placebo for PF-06865571 for each cohort.; Drug: PF-06865571; Multiple ascending dose of PF-06865571 as extemporaneously prepared suspension for 14 consecutive days with total daily dose of 90mg, 300mg, 900mg, 1800mg, 3000mg and TBD.
EXPERIMENTAL: Cohort 4_1800mg and Matching Placebo	Drug: Placebo; Matching Placebo for PF-06865571 for each cohort.; Drug: PF-06865571; Multiple ascending dose of PF-06865571 as extemporaneously prepared suspension for 14 consecutive days with total daily dose of 90mg, 300mg, 900mg, 1800mg, 3000mg and TBD.
EXPERIMENTAL: Cohort 5_3000mg and Matching Placebo	Drug: Placebo; Matching Placebo for PF-06865571 for each cohort.; Drug: PF-06865571; Multiple ascending dose of PF-06865571 as extemporaneously prepared suspension for 14 consecutive days with total daily dose of 90mg, 300mg, 900mg, 1800mg, 3000mg and TBD.
EXPERIMENTAL: Optional Cohort 6_TBD mg and Matching Placebo	Drug: Placebo; Matching Placebo for PF-06865571 for each cohort.; Drug: PF-06865571; Multiple ascending dose of PF-06865571 as extemporaneously prepared suspension for 14 consecutive days with total daily dose of 90mg, 300mg, 900mg, 1800mg, 3000mg and TBD.
EXPERIMENTAL: Optional Cohort 7_TBD mg and Matching Placebo	Drug: Placebo; Matching Placebo for PF-06865571 for each cohort.; Drug: PF-06865571; Multiple ascending dose of PF-06865571 as extemporaneously prepared suspension for 14 consecutive days with total daily dose of 90mg, 300mg, 900mg, 1800mg, 3000mg and TBD.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with adverse events (AEs)	Number of participants with reported adverse events	Baseline up to 35 days after last dose of study medication
Number of subjects with laboratory tests findings of potential clinical importance	Number of participants with potentially clinically important laboratory test findings	Baseline (Day 0) up to 24 days after last dose of study medication
Number of subjects with electrocardiogram (ECG) findings of potential clinical importance	Number of participants with potentially clinically important ECG findings	Baseline (Day 0) up to 24 days after last dose of study medication
Number of subjects with vital signs findings of potential clinical importance	Number of participants with potentially clinically important vital sign measurements	Baseline (Day 0) up to 24 days after last dose of study medication

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) for PF-06865571		0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hour post dose on Days 1, 7, and 14
AUCtau for PF-06865571	Area under the concentration-time curve calculated by linear trapezoidal rule from time zero to the end of the dosing interval (i.e., 24 h) at steady state.	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hour post dose on Days 1, 7, and 14
Time to Reach Maximum Observed Concentration for PF-06865571	Time to Reach Maximum Observed Plasma Concentration (Tmax)	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hour post dose on Days 1, 7, and 14
Dose normalized Cmax for PF-06865571	Following log-transformation, dose normalized Cmax will be analysed using a mixed model appropriate to the study design.	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hour post dose on Days 1, 7, and 14
Amount of unchanged drug recovered in urine during the dosing interval (Aetau) for PF-06865571	Sum of [urine concentration * sample volume] for each collection over the dosing interval	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hour post dose on Day 14
Percent of dose recovered in urine as unchanged drug (Aetau %) for PF-06865571	100* Aetau/Dose	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hour post dose on Day 14
Renal clearance (CLr) for PF-06865571	Aetau/AUCtau	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hour post dose on Day 14

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.
• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2017
• Primary Completion (ACTUAL): May 3, 2018
• Study Completion (ACTUAL): May 3, 2018

Study Registration Dates

• First Submitted: July 24, 2017
• First Submitted That Met QC Criteria: July 24, 2017
• First Posted (ACTUAL): July 26, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 23, 2018
• Last Update Submitted That Met QC Criteria: May 21, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Body Weight; Overweight
• Other Study ID Numbers: C2541002; 2017-001649-28 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_requests

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No