Clinical trial NCT02691702: Multiple Dose Study Of BIIB118 (PF-05251749) In Healthy Volunteers
Official title: A Phase 1, Double Blind, Sponsor Open, Randomized, Placebo And Active Comparator Controlled, Dose Escalation Study To Investigate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Escalating Doses Of Pf-05251749 In Healthy Adult And Elderly Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Adult Subjects
Healthy Elderly Subjects
Keywords: Multiple Ascending Dose Study
Safety and Tolerability
Pharmacokinetics
Pharmacodynamics
Melatonin
Plasma
Dim Light Melatonin Onset
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2016-02-25
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This is the first clinical trial to evaluate ascending multiple oral doses in healthy adult and healthy elderly subjects to characterize the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of BIIB118

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 (Parts A and B) or 65 and 85 years (Part C), 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: Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness
timeFrame: Baseline (0h on Day 1), Day 1 (2h), Day 4 (1.5h), Day 7 (0h, 2h), Day 10 (1.5h), Day 14 (0h, 2h), Day 15 (0h) and Day 16 (0h).
measure: Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness
timeFrame: Baseline (0h on Day 1), Day 1 (2h), Day 4 (1.5h), Day 7 (0h, 2h), Day 10 (1.5h), Day 14 (0h, 2h), Day 15 (0h) and Day 16 (0h).
measure: Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood
timeFrame: Baseline (0h on Day 1), Day 1 (2h), Day 4 (1.5h), Day 7 (0h, 2h), Day 10 (1.5h), Day 14 (0h, 2h), Day 15 (0h) and Day 16 (0h).
measure: Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Days 0, 7, 14, 16, and follow-up visit (28 calender days after the last dose of investigational product on Day 14).
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) (All Causalities)
timeFrame: Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) (Treatment Related)
timeFrame: Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
measure: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
timeFrame: Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
measure: Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values)
timeFrame: Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
measure: Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline)
timeFrame: Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
measure: Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline)
timeFrame: Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
measure: Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values)
timeFrame: Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
measure: Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline)
timeFrame: Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
measure: Number of Participants With New/Intensified Physical Examination Findings
timeFrame: Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
measure: Number of Participants With New/Intensified Neurological Examination Findings
timeFrame: Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14
timeFrame: Days 1 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h), 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).
measure: Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14.
timeFrame: Days 1 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h), 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).
measure: Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14
timeFrame: Days 1 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h), 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).
measure: Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14
timeFrame: Days 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).
measure: Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14
timeFrame: Days 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).
measure: Plasma Peak-to-trough Ratio (PTR) (Cmax/Cmin) of PF-05251749 - Days 7 and 14
timeFrame: Days 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).
measure: Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14
timeFrame: Days 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).
measure: Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14
timeFrame: Days 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).
measure: Terminal Half-Life (t1/2) of PF-05251749 - Day 14
timeFrame: Day 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).
measure: Apparent Volume of Distribution (Vz/F) of PF-05251749 - Day 14
timeFrame: Day 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).
measure: Cumulative Amount of Drug Recovered Unchanged in Urine Over Dosing Interval Tau (Aetau) of PF-05251749 - Day 14
timeFrame: Day 14 (0, 0.5, 1, 1.5, 2, 3, 4, 5, 8, 12, 16, 20, 24, 48h).
measure: Percentage of Dose Recovered Unchanged in Urine Over Dosing Interval Tau (Aetau%) of PF-05251749 - Day 14
timeFrame: Day 14 (0, 0.5, 1, 1.5, 2, 3, 4, 5, 8, 12, 16, 20, 24, 48h).
measure: Renal Clearance (CLr) of PF-05251749 - Day 14
timeFrame: Day 14 (0, 0.5, 1, 1.5, 2, 3, 4, 5, 8, 12, 16, 20, 24, 48h).
measure: Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 6
timeFrame: Day 0 (Baseline) and Day 6.
measure: Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 15
timeFrame: Day 0 (Baseline) and Day 15
Other outcomes:
Locations:
city: South Miami
country: United States
facility: QPS-MRA, LLC (Miami Research Associates)
state: Florida
city: South Miami
country: United States
facility: Qps-Mra, Llc
state: Florida
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: