Pharmacodynamic Study of BIIB095 and BIIB074 in Healthy Participants and Participants With Painful Diabetic Polyneuropathy

Phase 1

Withdrawn

• Conditions: Healthy Volunteers; Diabetic Neuropathies
• Interventions: Drug: BIIB095; Drug: Placebo; Drug: Lidocaine; Drug: BIIB074

• Registration Number: NCT04106050
• Lead Sponsor: Biogen

Brief Summary

Part A: Primary objective is to determine the effects of BIIB095 on nerve excitability in healthy participants. Secondary and exploratory objectives include determining the effects of BIIB095 on nerve excitability in diabetic polyneuropathy (DPN) and assessing the safety, tolerability and pharmacokinetics of BIIB095.

Part B (optional): Equivalent objectives are pursued for BIIB074.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-09-25
• Study First Submitted QC: 2019-09-25
• Study First Posted: 2019-09-26
• Study Start: 2020-09-30
• Status Verified: 2021-03
• Last Update Submitted: 2021-03-19
• Last Update Posted: 2021-03-22
• Primary Completion: 2022-01-21
• Study Completion: 2022-01-21

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Healthy participants must be in good health, as determined based on medical history and screening evaluations

• Participants with DPN

  • Must have a documented diagnosis of type 2 diabetes mellitus (DM)
  • Must have stable glycemic control
  • Must have at least clinical evidence of painful DPN
  • Pain related to DPN must be present for at least 6 months prior to screening
  • Average daily pain intensity over 7 consecutive days recorded during screening must be ≥ 4 on an 11-point numerical rating scale ranging from 0 (no pain) to 10 (worst pain imaginable)

Key

Exclusion Criteria

• Any neurologic or painful condition that could confound the interpretation of study results
• History of any clinically significant cardiac, hematologic, hepatic, immunologic, urologic, pulmonary, dermatologic, psychiatric, renal, or other major disease. This includes any clinically significant endocrinologic or neurologic disease other than DM or DPN.
• Use of local anesthetics or capsaicin for topical or regional treatment within 3 months prior to Screening.
• Systemic use of sodium channel inhibitors

Note: Other protocol-specific inclusion/exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part A: BIIB095 Dose 1	BIIB095	Healthy participants and participants with DPN will receive oral dose of BIIB095 Dose 1 capsules from Day 1 to Day 8.
Part A: BIIB095 Dose 2	BIIB095	Healthy participants and participants with DPN will receive oral dose of BIIB095 Dose 2 capsules from Day 1 to Day 8.
Part A: BIIB095 Dose 3	BIIB095	Healthy participants and participants with DPN will receive oral dose of BIIB095 Dose 3 capsules from Day 1 to Day 8.
Part A: BIIB095 Placebo	Placebo	Healthy participants and participants with DPN will receive oral dose of placebo matching BIIB095 capsules from Day 1 to Day 8.
Part A: Lidocaine	Lidocaine	Healthy participants and participants with DPN will receive single injection of lidocaine for partial nerve conduction block and single injection of lidocaine for skin infiltration on Day 8.
Part B: BIIB074 Dose 1	BIIB074	Healthy participants and participants with DPN will receive oral dose of BIIB074 Dose 1 tablets from Day 1 to Day 8.
Part B: BIIB074 Placebo	Placebo	Healthy participants and participants with DPN will receive oral dose of placebo matching BIIB074 tablets from Day 1 to Day 8.

Primary Outcome Measures

Name	Time	Method
Change in Nerve Excitability from Baseline (Day 1) to Last Treatment Visit (Day 8) as Determined by Compound Muscle Action Potential Threshold Tracking (CMAP-TT) in the Median Nerve of Healthy Participants	Baseline (Day 1), Day 8

Secondary Outcome Measures

Name	Time	Method
Change in Sensory Nerve Excitability from Baseline (Day 1) to Last Treatment Visit (Day 8) as Determined by Sensory Nerve Action Potential Threshold Tracking (SNAP-TT) in the Median Nerve of Healthy Participants	Baseline (Day 1), Day 8
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)	AEs: Day 1 up to Day 22; SAEs: Screening up to Day 22
Area Under the Curve from Time Zero to Time of the Last Measurable Concentration (AUClast)	Pre-dose, 1 hour (h), 1.5h, 3h, 6h and 8h post-dose on Day 8
Area Under the Curve within a Dosing Interval (AUCtau)	Pre-dose, 1 hour (h), 1.5h, 3h, 6h and 8h post-dose on Day 8
Maximum Observed Concentration (Cmax)	Pre-dose, 1 hour (h), 1.5h, 3h, 6h and 8h post-dose on Day 8
Trough Concentration (Ctrough)	Pre-dose, 1 hour (h), 1.5h, 3h, 6h and 8h post-dose on Day 8
Time to Reach Maximum Observed Concentration (Tmax)	Pre-dose, 1 hour (h), 1.5h, 3h, 6h and 8h post-dose on Day 8