Phase 1
Completed N=97
Multiple Dose Study Of BIIB118 (PF-05251749) In Healthy Volunteers
Healthy Adult Subjects · Healthy Elderly Subjects
Source: ClinicalTrials.gov NCT02691702 ↗
Enrolled (actual)
97
Serious AEs
1.0%
Results posted
Oct 2018
Primary outcomePrimary: Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness — 2.16; 7.50; 6.71; 3.50 Units on a scale
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
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness |
2.16; 7.50; 6.71; 3.50; 4.58; 4.05 | — |
| PRIMARY Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness |
0.70; 1.45; 3.56; 13.88; 1.56; 2.25 | — |
| PRIMARY Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood |
1.16; 5.16; 2.20; 2.03; 5.55; 3.25 | — |
| PRIMARY Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events (AEs) (All Causalities) |
4; 3; 3; 1; 5; 7 | — |
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events (AEs) (Treatment Related) |
1; 2; 2; 1; 1; 5 | — |
| PRIMARY Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) |
2; 8; 1; 2; 4; 4 | — |
| PRIMARY Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) |
0; 0; 0; 0; 1; 1 | — |
| PRIMARY Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) |
0; 0; 1; 1; 0; 0 | — |
| PRIMARY Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) |
2; 0; 1; 0; 1; 0 | — |
| PRIMARY Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With New/Intensified Physical Examination Findings |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With New/Intensified Neurological Examination Findings |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 |
346.1; 838.1; 1600; 2465; 3990; 219.4 | — |
| SECONDARY Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. |
1430; 3302; 6514; 14060; 26630; 1626 | — |
| SECONDARY Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 |
1.00; 1.00; 1.00; 1.00; 1.00; 1.75 | — |
| SECONDARY Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14 |
29.42; 23.49; 26.09; 25.08; 22.76; 27.76 | — |
| SECONDARY Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14 |
11.01; 27.35; 65.88; 114.9; 340.3; 19.48 | — |
| SECONDARY Plasma Peak-to-trough Ratio (PTR) (Cmax/Cmin) of PF-05251749 - Days 7 and 14 |
40.04; 35.54; 24.01; 25.37; 13.00; 12.29 | — |
| SECONDARY Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14 |
1.188; 1.289; 1.176; 1.160; 1.255; 1.169 | — |
| SECONDARY Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14 |
1.272; 1.160; 0.9898; 1.161; 1.155; 1.093 | — |
| SECONDARY Terminal Half-Life (t1/2) of PF-05251749 - Day 14 |
9.625; 9.630; 10.91; 9.940; 11.20; 10.62 | — |
| SECONDARY Apparent Volume of Distribution (Vz/F) of PF-05251749 - Day 14 |
419.3; 323.6; 363.9; 409.0; 353.6; 405.5 | — |
| SECONDARY Cumulative Amount of Drug Recovered Unchanged in Urine Over Dosing Interval Tau (Aetau) of PF-05251749 - Day 14 |
56710; 142900; 317900; 404900; 738300 | — |
| SECONDARY Percentage of Dose Recovered Unchanged in Urine Over Dosing Interval Tau (Aetau%) of PF-05251749 - Day 14 |
0.1133; 0.1429; 0.1591; 0.1013; 0.09849 | — |
| SECONDARY Renal Clearance (CLr) of PF-05251749 - Day 14 |
37.18; 33.76; 37.39; 29.73; 22.15 | — |
| SECONDARY Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 6 |
10.0; 3.3; 11.3; 37.5; 85.0; 124.3 | — |
| SECONDARY Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 15 |
40.0; -36.7; 56.3; 112.5; 100.0; 115.7 | — |
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:
- 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;
- Have undergone a documented hysterectomy and/or bilateral oophorectomy;
- 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.
Data sourced from ClinicalTrials.gov (NCT02691702). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.