Clinical trial NCT03943056: A Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of BIIB091, a Bruton's Tyrosine Kinase (BTK) Inhibitor, in Healthy Adult Participants
Official title: A Phase 1, Randomized, Blinded, Placebo-Controlled, Single- and Multiple-Ascending Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of BIIB091, a Bruton's Tyrosine Kinase (BTK) Inhibitor, in Healthy Adult Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2019-05-09
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple oral doses of BIIB091 in healthy participants.This study will also determine the effect of food on the single oral dose pharmacokinetic (PK).

Detailed description: Initial protocol recruitment and follow up was completed by 10 Jan 2020 with an optional cohort intended for completion by April 2020. Subsequently, a decision was made not to progress this optional cohort in light of COVID-19 which has resulted in a delay in reporting the actual completion date.

Eligibility criteria: Key Inclusion Criteria:

* Ability 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 applicable participant privacy regulations.
* Have a body mass index between 18 and 30 kg/m2, inclusive.
* All male participants must practice highly effective methods of contraception and not donate sperm during the study and for at least 1 spermatogenic cycle (90 days) after administration of last dose of study treatment.
* All female participants of childbearing potential must practice highly effective methods of contraception and not donate eggs during the study and for at least 90 days after their last dose of study treatment.
* Must be in good health as 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.
* History of severe allergic or anaphylactic reactions, or of any allergic reactions that in the opinion of the Investigator are likely to be exacerbated by any component of the study treatment.
* History of, or ongoing, malignant disease, including solid tumors and hematologic malignancies (with the exception of basal cell carcinomas and squamous cell carcinomas that have been completely excised and considered cured at least 12 months prior to Check-in).
* Current enrollment or plan to enroll in any other drug, biological, device, or clinical study, or treatment with an investigational drug or approved therapy for investigational use within 30 days prior to Check-in, or 5 half-lives of the drug or therapy, whichever is longer.
* Breastfeeding, pregnant, or planning to become pregnant during study participation.

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

Primary outcomes:
measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Day 9 for SAD Cohorts; Baseline up to Day 24 for MAD Cohorts
Secondary outcomes:
measure: Area Under the Curve from Time 0 to the Time of the Last Measurable Concentration (AUClast)
timeFrame: Baseline and multiple timepoints up to Day 3 for SAD Cohorts; Baseline and multiple timepoints up to Day 16 for MAD Cohorts
measure: Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf)
timeFrame: Baseline and multiple timepoints up to Day 3
measure: Maximum Observed Concentration (Cmax)
timeFrame: Baseline and multiple timepoints up to Day 3 for SAD Cohorts; Baseline and multiple timepoints up to Day 14 for MAD Cohorts
measure: Time to Reach Maximum Observed Concentration (Tmax)
timeFrame: Baseline and multiple timepoints up to Day 3 for SAD Cohorts; Baseline and multiple timepoints up to Day 14 for MAD Cohorts
measure: Elimination Half-Life (t½)
timeFrame: Baseline and multiple timepoints up to Day 3 for SAD Cohorts; Baseline and multiple timepoints up to Day 16 for MAD Cohorts
measure: Apparent Total Body Clearance (CL/F)
timeFrame: Baseline and multiple timepoints up to Day 3 for SAD Cohorts; Baseline and multiple timepoints up to Day 16 for MAD Cohorts
measure: Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F)
timeFrame: Baseline and multiple timepoints up to Day 3 for SAD Cohorts; Baseline and multiple timepoints up to Day 16 for MAD Cohorts
measure: Amount of BIIB091 Excreted in Urine per Sampling Interval (Aeu)
timeFrame: Baseline and multiple timepoints up to Day 3
measure: Percentage of BIIB091 Excreted in Urine per Sampling Interval (%Feu)
timeFrame: Baseline and multiple timepoints up to Day 3
measure: Renal clearance (CLr)
timeFrame: Baseline and multiple timepoints up to Day 3
measure: Area Under the Concentration-Time Curve Within a Dosing Interval (AUCtau)
timeFrame: Baseline and multiple timepoints up to Day 16
measure: Accumulation Ratio (R)
timeFrame: Baseline and multiple timepoints up to Day 16
measure: Trough concentration (Ctrough)
timeFrame: Baseline and multiple timepoints up to Day 16
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Research Site
state: Texas
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: