A Multiple Oral Doses Study Of PF-06427878 In Healthy Adult Subjects

• ClinicalTrials.gov Identifier: NCT02391623
• Recruitment Status: Completed
• First Posted: March 18, 2015
• Last Update Posted: March 2, 2016
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: March 12, 2015
• First Posted Date: March 18, 2015
• Last Update Posted Date: March 2, 2016
• Study Start Date: March 2015
• Actual Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 12, 2015)

• Assessment of adverse events (AEs). [ Time Frame: 0-25 days ]
• Assessment of clinical laboratory tests. [ Time Frame: 0-25 days ]
• Assessment of vital signs (including blood pressure and pulse rate). [ Time Frame: 0-25 days ]
• Assessment of cardiac conduction intervals as assessed via 12-lead electrocardiogram (ECG). [ Time Frame: 0-25 days ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 12, 2015)

• Maximum Observed Plasma Concentration (Cmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 1 [ Time Frame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose ]
• Maximum Observed Plasma Concentration (Cmax) for PF-06427878during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 12 [ Time Frame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose ]
• Maximum Observed Plasma Concentration (Cmax) for PF-06427878 on day 14 [ Time Frame: 0, 1, 2, 3, 4, 6, 8, 12 hours post dose ]
• Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 1 [ Time Frame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose ]
• Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 12 [ Time Frame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose ]
• Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 [ Time Frame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose ]
• Area Under the Curve for PF-06427878 during the dosing interval (AUCtau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 1 [ Time Frame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose ]
• Area Under the Curve for PF-06427878 during the dosing interval (AUCtau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 12 [ Time Frame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose ]
• Area Under the Curve for PF-06427878 during the dosing interval (AUCtau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 [ Time Frame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose ]
• Plasma Decay Half-Life (t1/2) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 [ Time Frame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose ]
• Apparent Volume of Distribution (Vz/F) of PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 [ Time Frame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose ]
• Apparent Oral Clearance (CL/F) of PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 [ Time Frame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose ]
• Minimum Observed Plasma Concentration (Cmin) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 [ Time Frame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose ]
• Peak:Trough ratio of PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 [ Time Frame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose ]
• Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06427878 on day14 relative to day 1 [ Time Frame: 0, 1, 2, 3, 4, 6, 8, 12 hours post dose ]
• Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06427878 on day14 relative to day 1 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD [ Time Frame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose ]
• Accumulation ratio for Area Under the Curve during the dosing interval (Rac(AUCtau)) for PF-06427878 on day14 relative to day 1 [ Time Frame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose ]
• Amount of PF-06427878 excreted in urine (Ae) during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 [ Time Frame: 0- tau hours post dose ]
• Percent of dose excreted in urine as PF-06427878 (Ae%) during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 [ Time Frame: 0- tau hours post dose ]
• Renal clearance of PF-06427878 (CLr) during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 [ Time Frame: 0- tau hours post dose ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Multiple Oral Doses Study Of PF-06427878 In Healthy Adult Subjects
• Official Title: A Phase 1, Randomized, Double-blind, Placebo-controlled Study To Assess The Safety, Tolerability, And Pharmacokinetics Of Multiple Escalating Oral Doses Of Pf-06427878 Co Administered With And Without Food In Healthy Adult Subjects
• Brief Summary: PF-06427878 is a new compound proposed for the treatment of hyperlipidemia. The primary purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of multiple oral doses of PF-06427878 in healthy adult subjects.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Basic Science
• Condition: Healthy Subjects

Intervention

• Drug: PF-06427878
  PF-06427878 will be administered as an extemporaneously prepared solution every 8 hours for 14 days (n=8).
• Drug: Placebo
  Placebo will be administered as an extemporaneously prepared solution every 8 hours for 14 days (n=2).
• Drug: PF-06427878
  PF-06427878 will be administered as an extemporaneously prepared solution every 12 hours for 14 days (n=8).
• Drug: Placebo
  Placebo will be administered as an extemporaneously prepared solution every 12 hours for 14 days (n=2).

Study Arms

• Experimental: Cohort 1
  Single dose level of PF-06427878 at 5 mg or placebo every 8 hours (Q8H) for 14 days to investigate the safety, tolerability, and pharmacokinetics.
  Interventions:

  • Drug: PF-06427878
  • Drug: Placebo
• Experimental: Cohort 2
  Single dose level of PF-06427878 at a dose no more than 3.5-fold increase from Cohort 1 or placebo every 8 hours (Q8H) for 14 days to investigate the safety, tolerability, and pharmacokinetics.
  Interventions:

  • Drug: PF-06427878
  • Drug: Placebo
• Experimental: Cohort 3
  Single dose level of PF-06427878 at a dose no more than 3.5-fold increase from Cohort 2 or placebo every 8 hours (Q8H) for 14 days to investigate the safety, tolerability, and pharmacokinetics.
  Interventions:

  • Drug: PF-06427878
  • Drug: Placebo
• Experimental: Cohort 4
  Single dose level of PF-06427878 at a dose no more than 3.5-fold increase from Cohort 3 or placebo every 8 hours (Q8H) for 14 days to investigate the safety, tolerability, and pharmacokinetics.
  Interventions:

  • Drug: PF-06427878
  • Drug: Placebo
• Experimental: Cohort 5
  Single dose level of PF-06427878 at a dose no more than 3.5-fold increase from Cohort 4 or placebo every 8 hours (Q8H) for 14 days to investigate the safety, tolerability, and pharmacokinetics.
  Interventions:

  • Drug: PF-06427878
  • Drug: Placebo
• Experimental: Cohort 6
  Single dose level of PF-06427878 (with the same total daily dose as Cohort 5) or placebo every 12 hours (Q12H) for 14 days to investigate the safety, tolerability, and pharmacokinetics.
  Interventions:

  • Drug: PF-06427878
  • Drug: Placebo

• Publications *: Amin NB, Carvajal-Gonzalez S, Purkal J, Zhu T, Crowley C, Perez S, Chidsey K, Kim AM, Goodwin B. Targeting diacylglycerol acyltransferase 2 for the treatment of nonalcoholic steatohepatitis. Sci Transl Med. 2019 Nov 27;11(520). pii: eaav9701. doi: 10.1126/scitranslmed.aav9701.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 1, 2016): 40
• Original Estimated Enrollment (submitted: March 12, 2015): 60
• Actual Study Completion Date: February 2016
• Actual Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Healthy male and/or female subjects of non childbearing potential.
• Body Mass Index (BMI) of 17.5 to 35.4 kg/m2; and a total body weight >50 kg
• Subjects with fasting TG level of >=90 mg/dL and <=500 mg/dL following an overnight fast
• Subjects with low density lipoprotein cholesterol between 115 mg/dL and 190 mg/dL following an overnight fast

Exclusion Criteria:

•Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium

Administrative Information

• NCT Number: NCT02391623
• Other Study ID Numbers: B7871002; 2015-000130-29 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: March 2016