Evaluating the Safety, Tolerability, and Pharmacokinetics of BIIB095 in Healthy Participants

A Phase 1, Randomized, Double-Blinded, Placebo-Controlled, Single- and Multiple-Ascending Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BIIB095 in Healthy Subjects

The primary objective of the study is to evaluate the safety and tolerability of single- and multiple-ascending oral doses of BIIB095 in healthy participants. The secondary objectives are to characterize the single- and multiple-oral-dose PK of BIIB095 in healthy participants and to investigate the effect of food on the single-oral-dose PK of BIIB095 in healthy participants.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: Placebo; Drug: BIIB095

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS2 9LH
    • Research Site
  • London, United Kingdom, NW10 7EW
    • Hammersmith Medicines Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Ability of the subject to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local subject privacy regulations.
• Must have a body mass index between 18 and 30 kg/m2, inclusive.
• All women of childbearing potential and all men must practice highly effective contraception during the study and for 5 times the half-life or 3 months, whichever is longer, after their last dose of study treatment. In addition, subjects should not donate sperm or eggs during the study and for at least 3 months after their last dose of study treatment.
• Must be in good health as determined by the Investigator, based on medical history and Screening evaluations.

Key Exclusion Criteria:

• History of any clinically significant cardiac, endocrine, gastrointestinal, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, or renal disease, or other major disease, as determined by the Investigator.
• Significant history of fainting or vaso-vagal attacks, as determined by the Investigator.
• Current condition known to affect cardiac conduction, or a personal or familial history of Brugada syndrome.
• Congenital nonhemolytic hyperbilirubinemia (Gilbert's syndrome).
• History or risk of seizures or a history of epilepsy, significant head injury or related neurological disorders (excluding childhood febrile convulsions), as determined by the Investigator.
• Current enrollment in any other drug, biologic, device, or clinical study, or treatment with an investigational drug or approved therapy for investigational use within 30 days (6 months for biologics) prior to Day -1, or 5 half-lives of the agent, whichever is longer.
• Exposure to more than 4 experimental chemical entities within 12 months prior to the first dosing day.
• Breastfeeding, pregnant, or planning to become pregnant during study participation

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: BIIB095 5 mg; Following an overnight fast from food of at least 8 hours, participants will receive a single dose of either BIIB095 5 mg or placebo orally, followed by a fast of at least 4 hours post dose.	Drug: Placebo; Administered as specified in the treatment arm.; Drug: BIIB095; Administered as specified in the treatment arm.
Experimental: Cohort 2: BIIB095 25 mg; Following an overnight fast from food of at least 8 hours, participants will receive a single dose of either BIIB095 25 mg or placebo orally, followed by a fast of at least 4 hours post dose.	Drug: Placebo; Administered as specified in the treatment arm.; Drug: BIIB095; Administered as specified in the treatment arm.
Experimental: Cohort 3: BIIB095 100 mg; Following an overnight fast from food of at least 8 hours, participants will receive a single dose of either BIIB095 100 mg or placebo orally, followed by a fast of at least 4 hours post dose.	Drug: Placebo; Administered as specified in the treatment arm.; Drug: BIIB095; Administered as specified in the treatment arm.
Experimental: Cohort 4 (Fasted): BIIB095 200 mg; Following an overnight fast from food of at least 8 hours, participants will receive a single dose of either BIIB095 200 mg or placebo orally, followed by a fast of at least 4 hours post dose.	Drug: Placebo; Administered as specified in the treatment arm.; Drug: BIIB095; Administered as specified in the treatment arm.
Experimental: Cohort 4 (Fed): BIIB095 200 mg; After a minimum 2 week washout period, followed by an overnight fast of at least 8 hours, participants will consume a high fat breakfast. Participants will then receive a single dose of either BIIB095 200 mg or placebo orally within 30 minutes after starting the breakfast, followed by a fast from food for at least 4 hours post dose.	Drug: Placebo; Administered as specified in the treatment arm.; Drug: BIIB095; Administered as specified in the treatment arm.
Experimental: Cohort 5: BIIB095 400 mg; Following an overnight fast from food of at least 8 hours, participants will receive a single dose of either BIIB095 400 mg or placebo orally, followed by a fast of at least 4 hours post dose.	Drug: Placebo; Administered as specified in the treatment arm.; Drug: BIIB095; Administered as specified in the treatment arm.
Experimental: Cohort 6: BIIB095 600 mg; Following an overnight fast from food of at least 8 hours, participants will receive a single dose of either BIIB095 600 mg or placebo orally, followed by a fast of at least 4 hours post dose.	Drug: Placebo; Administered as specified in the treatment arm.; Drug: BIIB095; Administered as specified in the treatment arm.
Experimental: Cohort 7: BIIB095 50 mg BID; Participants will receive a single dose of either BIIB095 50 mg or placebo orally BID approximately 12 hours apart from Days 1 to 13, and once in the morning on Day 14. Morning doses will be preceded by an overnight fast from food of at least 8 hours and will be followed by a fast of at least 2 hours post dose. Evening doses will be preceded by a fast from food of at least 2 hours and will be followed by a fast of at least 2 hours post dose.	Drug: Placebo; Administered as specified in the treatment arm.; Drug: BIIB095; Administered as specified in the treatment arm.
Experimental: Cohort 8: BIIB095 100 mg BID; Participants will receive a single dose of either BIIB095 100 mg or placebo orally BID approximately 12 hours apart from Days 1 to 13, and once in the morning on Day 14. Morning doses will be preceded by an overnight fast from food of at least 8 hours and will be followed by a fast of at least 2 hours post dose. Evening doses will be preceded by a fast from food of at least 2 hours and will be followed by a fast of at least 2 hours post dose.	Drug: Placebo; Administered as specified in the treatment arm.; Drug: BIIB095; Administered as specified in the treatment arm.
Experimental: Cohort 9: BIIB095 200 mg BID; Participants will receive a single dose of either BIIB095 200 mg or placebo orally BID approximately 12 hours apart from Days 1 to 13, and once in the morning on Day 14. Morning doses will be preceded by an overnight fast from food of at least 8 hours and will be followed by a fast of at least 2 hours post dose. Evening doses will be preceded by a fast from food of at least 2 hours and will be followed by a fast of at least 2 hours post dose.	Drug: Placebo; Administered as specified in the treatment arm.; Drug: BIIB095; Administered as specified in the treatment arm.
Experimental: Cohort 10: BIIB095 300 mg BID; Participants will receive a single dose of either BIIB095 300 mg or placebo orally BID approximately 12 hours apart from Days 1 to 13, and once in the morning on Day 14. Morning doses will be preceded by an overnight fast from food of at least 8 hours and will be followed by a fast of at least 2 hours post dose. Evening doses will be preceded by a fast from food of at least 2 hours and will be followed by a fast of at least 2 hours post dose.	Drug: Placebo; Administered as specified in the treatment arm.; Drug: BIIB095; Administered as specified in the treatment arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with Serious Adverse Events (SAEs)	An SAE is any untoward medical occurrence that at any dose: Results in death; in the view of the Investigator, places the participant at immediate risk of death (a life threatening event), however, this does not include an event that, had it occurred in a more severe form, might have caused death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is a medically important event	Signing of Informed Consent (<=28 Days Prior to Day -1, Check-in) to End of Study (Up to 40 Days for Single-Ascending Dose (SAD) Cohorts 1-3 and 5-6; at Least 59 Days for SAD Cohort 4; Up to 53 Days for Multiple-Ascending Dose (MAD) Cohorts 7-10)
Percentage of Participants with Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.	Signing of Informed Consent (<=28 Days Prior to Day -1, Check-in) to End of Study (Up to 40 Days for Single-Ascending Dose (SAD) Cohorts 1-3 and 5-6; at Least 59 Days for SAD Cohort 4; Up to 53 Days for Multiple-Ascending Dose (MAD) Cohorts 7-10)
Percentage of Participants with Clinically Significant Abnormalities in Clinical Laboratory Assessments		Signing of Informed Consent (<=28 Days Prior to Day -1, Check-in) to End of Study (Up to 40 Days for Single-Ascending Dose (SAD) Cohorts 1-3 and 5-6; at Least 59 Days for SAD Cohort 4; Up to 53 Days for Multiple-Ascending Dose (MAD) Cohorts 7-10)
Percentage of Participants with Clinically Significant Abnormalities in Vital Signs		Signing of Informed Consent (<=28 Days Prior to Day -1, Check-in) to End of Study (Up to 40 Days for Single-Ascending Dose (SAD) Cohorts 1-3 and 5-6; at Least 59 Days for SAD Cohort 4; Up to 53 Days for Multiple-Ascending Dose (MAD) Cohorts 7-10)
Percentage of Participants with Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG) Parameters		Signing of Informed Consent (<=28 Days Prior to Day -1, Check-in) to End of Study (Up to 40 Days for Single-Ascending Dose (SAD) Cohorts 1-3 and 5-6; at Least 59 Days for SAD Cohort 4; Up to 53 Days for Multiple-Ascending Dose (MAD) Cohorts 7-10)
Percentage of Participants with Clinically Significant Abnormalities in Physical Examinations		Signing of Informed Consent (<=28 Days Prior to Day -1, Check-in) to End of Study (Up to 40 Days for Single-Ascending Dose (SAD) Cohorts 1-3 and 5-6; at Least 59 Days for SAD Cohort 4; Up to 53 Days for Multiple-Ascending Dose (MAD) Cohorts 7-10)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-Time Curve (AUC) from Time Zero to the Time of the Last Measurable Concentration (AUClast)	Pharmacokinetic (PK) parameter calculated to assess the PK of BIIB095 in blood.	Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts
AUC from Time Zero Extrapolated to Infinity (AUC∞)	Pharmacokinetic (PK) parameter calculated to assess the PK of BIIB095 in blood.	Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts
AUC Within a Dosing Interval (AUCtau)	Pharmacokinetic (PK) parameter calculated to assess the PK of BIIB095 in blood.	Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts
Maximum Observed Concentration (Cmax)	Pharmacokinetic (PK) parameter calculated to assess the PK of BIIB095 in blood.	Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts
Trough Concentration (Ctrough)	Pharmacokinetic (PK) parameter calculated to assess the PK of BIIB095 in blood.	Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts
Time to Cmax (Tmax)	Pharmacokinetic (PK) parameter calculated to assess the PK of BIIB095 in blood.	Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts
Terminal Elimination Half-Life (t1/2)	Pharmacokinetic (PK) parameter calculated to assess the PK of BIIB095 in blood.	Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts
Apparent Total Body Clearance (CL/F)	Pharmacokinetic (PK) parameter calculated to assess the PK of BIIB095 in blood.	Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts
Apparent Volume of Distribution (Vz/F)	Pharmacokinetic (PK) parameter calculated to assess the PK of BIIB095 in blood.	Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts
Accumulation Ratio (AR)	Pharmacokinetic (PK) parameter calculated to assess the PK of BIIB095 in blood.	Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts
Amount (Aeu) Excreted in Urine	Pharmacokinetic (PK) parameter calculated to assess the PK of BIIB095 in blood.	Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts
Percentage (%fe) Excreted in Urine	Pharmacokinetic (PK) parameter calculated to assess the PK of BIIB095 in blood.	Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts

Collaborators and Investigators

• Sponsor: Biogen

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2018
• Primary Completion (Actual): April 30, 2019
• Study Completion (Actual): April 30, 2019

Study Registration Dates

• First Submitted: February 27, 2018
• First Submitted That Met QC Criteria: February 27, 2018
• First Posted (Actual): March 5, 2018

Study Record Updates

• Last Update Posted (Actual): May 16, 2019
• Last Update Submitted That Met QC Criteria: May 15, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Healthy volunteers; Chronic pain; Neuropathic pain; Neuralgia
• Other Study ID Numbers: 255HV101; 2017-003982-90 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No