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

Healthy Volunteer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03454126
• Other study ID #: 255HV101
• Secondary ID: 2017-003982-90
• Status: Completed
• Phase: Phase 1
• Start date: March 29, 2018
• Est. completion date: April 30, 2019

Study information

• Verified date: May 2019
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: April 30, 2019
• Est. primary completion date: April 30, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Drug:
• BIIB095
Administered as specified in the treatment arm.
• Placebo
Administered as specified in the treatment arm.

Locations

Country	Name	City	State
United Kingdom	Research Site	Leeds
United Kingdom	Hammersmith Medicines Research	London

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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
Secondary	AUC from Time Zero Extrapolated to Infinity (AUC8)	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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