Clinical trial NCT02443740: Safety, Tolerability and Pharmacokinetics of BIIB118 (PF-05251749)
Official title: A Phase 1, Randomized, Double Blind, Placebo Controlled Study To Investigate The Safety, Tolerability, Pharmacokinetics And Relative Bioavailability Of Single Escalating Oral Doses Of Pf-05251749 In Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: First in human
Single Ascending Dose Study
Safety and Tolerability
Pharmacokinetics
Plasma
Cerebrospinal Fluid
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2015-05-14
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This is a First in human (FIH) single ascending dose study to evaluate the safety, tolerability and pharmacokinetics (PKs) of BIIB118 following single oral doses in healthy human subjects

Detailed description: This study was previously posted by Pfizer. In March, 2020, sponsorship of the trial was transferred to Biogen.

Eligibility criteria: Inclusion Criteria:

•Healthy male and/or female subjects of non-childbearing potential between the ages of 18 and 55 years, inclusive (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests).

Female subjects of non-childbearing potential must meet at least one of the following criteria:

1. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle-stimulating hormone (FSH) level confirming the post-menopausal state;
2. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
3. Have medically confirmed ovarian failure. All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy, bilateral oophorectomy and/or ovarian failure) will be considered to be of childbearing potential.

   * Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lbs).
   * Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
   * Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

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).
* Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study medication (whichever is longer).
* Screening supine blood pressure \>= 140 mm Hg (systolic) or \>=90 mm Hg (diastolic), following at least 5 minutes of rest. If BP is \>=140 mm Hg (systolic) or \>=90 mm Hg (diastolic), repeat per local standard operating procedures (SOP). If orthostatic changes are present and deemed to be clinically significant by the investigator, Subject can be excluded.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: For Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3
measure: Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Findings
timeFrame: Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3
measure: Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2
timeFrame: Baseline, Day 1: 2 hours post dose
measure: Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2
timeFrame: Baseline, Day 1: 6 hours post dose
measure: Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2
timeFrame: Baseline, Day 3: 48 hours post dose
measure: Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2
timeFrame: Baseline, Day 1: 2 hours post dose
measure: Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2
timeFrame: Baseline, Day 1: 48 hours post dose
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of PF-05251749
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05251749
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-05251749
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05251749
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose
measure: Plasma Decay Half-Life (t1/2) of PF-05251749
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose
measure: Apparent Oral Clearance (CL/F) of PF-05251749
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose
measure: Apparent Volume of Distribution (Vz/F) of PF-05251749
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Milled and Unmilled PF-05251749: Cohort 4
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Milled and Unmilled PF-05251749: Cohort 4
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose
measure: Maximum Observed Plasma Concentration (Cmax) of Milled and Unmilled PF-05251749: Cohort 4
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Milled and Unmilled PF-05251749: Cohort 4
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose
measure: Area Under the Curve From Time Zero to Last Quantifiable Cerebrospinal Fluid (CSF) Concentration (AUClast) of PF-05251749
timeFrame: Predose, 1.5, 2.5, 4, and 8 hours post dose
measure: Area Under the Curve From Time Zero to Extrapolated Cerebrospinal Fluid (CSF) Infinite Time [AUC (0 - ∞)] of PF-05251749
timeFrame: Predose, 1.5, 2.5, 4, and 8 hours post dose
measure: Maximum Observed Cerebrospinal Fluid (CSF) Concentration (Cmax) of PF-05251749
timeFrame: Predose, 1.5, 2.5, 4, and 8 hours post dose
measure: Time to Reach Maximum Observed Cerebrospinal Fluid (CSF) Concentration (Tmax) of PF-05251749
timeFrame: Predose, 1.5, 2.5, 4, and 8 hours post dose
Other outcomes:
Locations:
city: New Haven
country: United States
facility: New Haven Clinical Research Unit
state: Connecticut
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: