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

A Phase 1b, Randomized, Double-Blind, Parallel, Placebo- and Active-Controlled, Pharmacodynamic Study of BIIB095 and BIIB074 in Healthy Participants and Participants With Painful Diabetic Polyneuropathy

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.

Study Overview

• Status: Withdrawn
• Conditions: Diabetic Neuropathies; Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: BIIB095; Drug: BIIB074; Drug: Lidocaine

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part A: BIIB095 Dose 1; Healthy participants and participants with DPN will receive oral dose of BIIB095 Dose 1 capsules from Day 1 to Day 8.	Drug: BIIB095; Administered as specified in the treatment arm.
EXPERIMENTAL: Part A: BIIB095 Dose 2; Healthy participants and participants with DPN will receive oral dose of BIIB095 Dose 2 capsules from Day 1 to Day 8.	Drug: BIIB095; Administered as specified in the treatment arm.
EXPERIMENTAL: Part A: BIIB095 Dose 3; Healthy participants and participants with DPN will receive oral dose of BIIB095 Dose 3 capsules from Day 1 to Day 8.	Drug: BIIB095; Administered as specified in the treatment arm.
PLACEBO_COMPARATOR: Part A: BIIB095 Placebo; Healthy participants and participants with DPN will receive oral dose of placebo matching BIIB095 capsules from Day 1 to Day 8.	Drug: Placebo; Administered as specified in the treatment arm.
ACTIVE_COMPARATOR: Part A: 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.	Drug: Lidocaine; Administered as specified in the treatment arm.
EXPERIMENTAL: Part B: BIIB074 Dose 1; Healthy participants and participants with DPN will receive oral dose of BIIB074 Dose 1 tablets from Day 1 to Day 8.	Drug: BIIB074; Administered as specified in the treatment arm.
PLACEBO_COMPARATOR: Part B: BIIB074 Placebo; Healthy participants and participants with DPN will receive oral dose of placebo matching BIIB074 tablets from Day 1 to Day 8.	Drug: Placebo; Administered as specified in the treatment arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Biogen

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): September 30, 2020
• Primary Completion (ANTICIPATED): January 21, 2022
• Study Completion (ANTICIPATED): January 21, 2022

Study Registration Dates

• First Submitted: September 25, 2019
• First Submitted That Met QC Criteria: September 25, 2019
• First Posted (ACTUAL): September 26, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 22, 2021
• Last Update Submitted That Met QC Criteria: March 19, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Neuromuscular Diseases; Peripheral Nervous System Diseases; Polyneuropathies; Diabetic Neuropathies; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lidocaine
• Other Study ID Numbers: 255NP101; 2019-001900-39 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on http://clinicalresearch.biogen.com/

Drug and device information, study documents

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