Clinical trial NCT03210961: A First in Human Study to Evaluate Safety, Tolerability, and Pharmacology of PF-06826647 in Healthy Subjects and Subjects With Plaque Psoriasis
Official title: A PHASE 1, WITHIN COHORT, RANDOMIZED, DOUBLE BLIND, THIRD-PARTY OPEN, PLACEBO-CONTROLLED, SINGLE- AND MULTIPLE DOSE ESCALATION, PARALLEL GROUP STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF PF-06826647 IN HEALTHY SUBJECTS AND SUBJECTS WITH PLAQUE PSORIASIS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Plaque Psoriasis
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2017-07-07
Enrollment: 109
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Combination single and multiple ascending dose design. Cohorts of participants are assigned to receive interventions based on acceptable safety, tolerability, and pharmacokinetics of previous dose cohort
Primary purpose: TREATMENT

Brief summary: This first in human study will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-06826647 in healthy subjects and subjects with plaque psoriasis.


Eligibility criteria: Healthy Participants:

Inclusion Criteria:

* Healthy male subjects between ages of 18-55 years
* Healthy female subjects of non-childbearing potential between the ages of 18-55 years
* Body Mass Index (BMI) of 17.5 to 30.5kg/m2; and a total body weight \>50kg (110lbs).
* No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB)
* (Optional) Japanese subjects who have four Japanese biologic grandparents born in Japan

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)
* Pregnant female subjects; breastfeeding female subjects; female subjects of childbearing potential
* 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
* Have a clinically significant infection currently or within 6 months of first dose of study drug

Psoriasis Participants:

Inclusion Criteria:

* Healthy male subjects between ages of 18-65 years
* Healthy female subjects of non-childbearing potential between the ages of 18-65 years
* Have a diagnosis of plaque psoriasis for at least 6 months prior to first study dose
* Have plaque-type psoriasis covering at least 15% of total body surface area (BSA) at Day-1(prior to randomization in the study
* No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB)

Exclusion Criteria:

* Currently have non-plaque forms of psoriasis, eg, erythrodermic, guttate, or pustular psoriasis
* Have a clinically significant infection currently or within 6 months of first dose of study drug, or a history of chronic or recurrent infectious disease
* Pregnant female subjects; breastfeeding female subjects; female subjects of childbearing potential
* 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

Primary outcomes:
measure: Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria (Single Ascending Dose [SAD] Period)
timeFrame: Baseline up to Day 8
measure: Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria (Multiple Ascending Dose [MAD] Period)
timeFrame: Baseline up to Day 28
measure: Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria (Psoriasis Cohorts)
timeFrame: Baseline up to Day 56
measure: Number of Participants With Physical Examination Data Meeting Pre-Specified Criteria (SAD Period)
timeFrame: Baseline up to Day 8
measure: Number of Participants With Physical Examination Data Meeting Pre-Specified Criteria (MAD Period)
timeFrame: Baseline up to Day 28
measure: Number of Participants With Physical Examination Data Meeting Pre-Specified Criteria (Psoriasis Cohorts)
timeFrame: Baseline up to Day 56
measure: Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria (SAD Period)
timeFrame: Baseline up to Day 8
measure: Number of Participants With ECG Data Meeting Pre-Specified Criteria (MAD Period)
timeFrame: Baseline up to Day 28
measure: Number of Participants With ECG Data Meeting Pre-Specified Criteria (Psoriasis Cohorts)
timeFrame: Baseline up to Day 56
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Who Withdrew Due to Adverse Events (AEs) (SAD Period)
timeFrame: Baseline up to Day 8
measure: Number of Participants With TEAEs, SAEs, and Who Withdrew Due to AEs (MAD Period)
timeFrame: Baseline up to Day 28
measure: Number of Participants With TEAEs, SAEs, and Who Withdrew Due to AEs (Psoriasis Cohorts)
timeFrame: Baseline up to Day 84
measure: Number of Participants With Laboratory Abnormalities (SAD Period)
timeFrame: Baseline up to Day 8
measure: Number of Participants With Laboratory Abnormalities (MAD Period)
timeFrame: Baseline up to Day 28
measure: Number of Participants With Laboratory Abnormalities (Psoriasis Cohorts)
timeFrame: Baseline up to Day 56
measure: Change in 24 Hour Creatinine Clearance From Day -1 on Day 10 (MAD Period)
timeFrame: Day -1 and Day 10
Secondary outcomes:
measure: Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) (SAD Period)
timeFrame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
measure: Secondary: Dose Normalized AUCinf (AUCinf[dn]) (SAD Period)
timeFrame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
measure: Area Under the Concentration-Time Profile From Time 0 to 24 Hours (AUC24) (SAD Period)
timeFrame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
measure: Area Under the Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) (SAD Period)
timeFrame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
measure: Dose Normalized AUClast (AUClast[dn]) (SAD Period)
timeFrame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
measure: Maximum Plasma Concentration (Cmax) (SAD Period)
timeFrame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
measure: Dose Normalized Cmax (Cmax[dn]) (SAD Period)
timeFrame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
measure: Time for Cmax (Tmax) (SAD Period)
timeFrame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
measure: Terminal Elimination Half-Life ((t½) (SAD Period)
timeFrame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
measure: Mean Residence Time (MRT) (SAD Period)
timeFrame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
measure: Apparent Volume of Distribution (Vz/F) (SAD Period)
timeFrame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
measure: Apparent Clearance (CL/F) (SAD Period)
timeFrame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
measure: Area Under the Plasma Concentration-Time Profile Over the Dosing Interval τ (AUCτ) (MAD Period Day 1)
timeFrame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
measure: Dose Normalized AUCτ (AUCτ[dn]) (MAD Period Day 1)
timeFrame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
measure: Cmax (MAD Period Day 1)
timeFrame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
measure: Cmax(dn) (MAD Period Day 1)
timeFrame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
measure: Tmax (MAD Period Day 1)
timeFrame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
measure: AUCτ (MAD Period Day 10)
timeFrame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
measure: AUCτ(dn) (MAD Period Day 10)
timeFrame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
measure: Cmax (MAD Period Day 10)
timeFrame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
measure: Cmax(dn) (MAD Period Day 10)
timeFrame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
measure: Tmax (MAD Period Day 10)
timeFrame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
measure: Average Concentration at Steady State (Cav) (MAD Period Day 10)
timeFrame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
measure: Lowest Concentration Observed During the Dosing Interval τ (Cmin) (MAD Period Day 10)
timeFrame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
measure: Terminal Elimination Half-Life ((t½) (MAD Period Day 10)
timeFrame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24,48,72,96,168 hours post-dose
measure: MRT (MAD Period Day 10)
timeFrame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24,48,72,96,168 hours post-dose
measure: Peak Trough Ratio (PTR) (MAD Period Day 10)
timeFrame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
measure: Observed Accumulation Ratio Based on AUC (Rac) (MAD Period Day 10)
timeFrame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
measure: Observed Accumulation Ratio Based on Cmax (Rac,Cmax) (MAD Period Day 10)
timeFrame: Days 1 and 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
measure: Vz/F (MAD Period Day 10)
timeFrame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
measure: CL/F (MAD Period Day 10)
timeFrame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
measure: Cumulative Amount of Drug Recovered Unchanged in Urine From Time 0 to the Dosing Interval τ Hours Post-Dose (Aeτ) (MAD Period Day 10)
timeFrame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
measure: Percentage of Dose Recovered Unchanged in Urine From Time 0 to the Dosing Interval τ Hours Post-Dose (Aeτ%) (MAD Period Day 10)
timeFrame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
measure: Renal Clearance (Clr) (MAD Period Day 10)
timeFrame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
measure: AUCτ (Psoriasis Cohorts)
timeFrame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
measure: AUCτ(dn) (Psoriasis Cohorts)
timeFrame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
measure: Cmax (Psoriasis Cohorts)
timeFrame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
measure: Cmax(dn) (Psoriasis Cohorts)
timeFrame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
measure: Tmax (Psoriasis Cohorts)
timeFrame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
measure: Cav (Psoriasis Cohorts)
timeFrame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
measure: Cmin (Psoriasis Cohorts)
timeFrame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
measure: Terminal Elimination Half-Life ((t½) (Psoriasis Cohorts)
timeFrame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24,168 hours post-dose
measure: MRT (Psoriasis Cohorts)
timeFrame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24,168 hours post-dose
measure: PTR (Psoriasis Cohorts)
timeFrame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
measure: Vz/F (Psoriasis Cohorts)
timeFrame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
measure: CL/F (Psoriasis Cohorts)
timeFrame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
measure: Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at Day 28
timeFrame: Baseline and Day 28
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: