A Phase IIa Withdrawal Study of CNV1014802 in Patients With Trigeminal Neuralgia

NCT01540630 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: CNV1014802/202
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

This is a double-blind, randomized withdrawal study comparing CNV1014802 with placebo in patients with trigeminal neuralgia who have successfully responded to CNV1014802 in an initial open-label phase. Patients will participate in an initial open-label treatment period of 21 days of CNV1014802 150mg three times a day (tid). Responders will be randomized to 28 days of CNV1014802 150mg tid or placebo. Following an interim analysis after 10 evaluable patients have completed the open-label phase, the dose regimen may be increased to 350mg twice a day (bid) for the remainder of the trial if the responder rate is less than 60%.

Conditions

Trigeminal Neuralgia

Outcome Measures

Primary Outcomes (1)

• The number of failures on CNV1014802 vs. number of failures on placebo during the double-blind treatment period will be the primary outcome of the study.

  Patients will be classified as a treatment failure if they meet one of the following criteria: * 50% increase in the frequency of paroxysms compared to the final 7 days of the open-label period * 50% increase in the severity of pain experienced in the paroxysms compared to the final 7 days of the open-label period * A Patient Global Improvement of Change rating of much worse/very much worse * The patient discontinues the study due to 'Lack of Efficacy'. v. The patient discontinues due to an adverse reaction or poor tolerability considered to be related to study medication

  4 weeks

Secondary Outcomes (1)

• Secondary pain endpoints

  4 weeks

Study Arms (2)

CNV1014802

EXPERIMENTAL

Drug: CNV1014802

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

CNV1014802 DRUG

CNV1014802 150mg tid for 28 days. Dose may be increased to 350mg bid following interim evaluation of efficacy.

CNV1014802

Placebo DRUG

Double-blind placebo comparator for 28 days.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged between 18 and 70 years, with a diagnosis of trigeminal neuralgia; IHS criteria to be used.
• Female patients must be of non-child bearing potential or agree to use an approved form of contraception
• Male patients must agree to use an approved form of contraception
• Body weight \> 50 kg for men and \> 45 kg for women.
• BMI ≤ 34.9
• Capable of giving written informed consent. Informed consent must be obtained prior to the commencement of any study related procedures.
• QTcB either/or QTcF \< 450 msec in two of three ECGs conducted at screening
• AST and ALT \< 2xULN; alkaline phosphatase and bilirubin \< 1.5xULN.
• Approved concomitant medications must have been stable for at least 3 weeks prior to day 0.

You may not qualify if:

• Patients who are known non-responders to sodium channel blockers at therapeutic doses.
• A positive pre-study drug screen.
• A positive history of HIV.
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• History of any liver disease within the last 6 months, with the exception of known Gilbert's disease.
• History of excessive regular alcohol consumption within 6 months of the study.
• Patients with a history or risk of seizures or a history of epilepsy, head injury or related neurological disorders
• Patients with a history of uncontrolled or poorly controlled hypertension, with systolic BP frequently exceeding 160mmHg and/or diastolic BP frequently exceeding 100mmHg, or patients who have BP greater than or equal to 160mmHg systolic and/or greater than or equal to 100mmHg diastolic at screening after repeated measurements
• History or presence of significant cardiovascular, gastro-intestinal, or renal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
• Patients with conditions known to affect cardiac conduction or a personal or familial history of Brugada syndrome
• Pregnant females or lactating females.
• History or presence of any clinically significant abnormality in vital signs/ECG/laboratory tests or have any medical or psychiatric condition, which, in the opinion of the Investigator may interfere with the study procedures or compromise patient safety.
• History of suicidal ideation and/or suicide attempts or clinical evidence of recent major depression.
• Patients who are unable to maintain approved medications for their trigeminal neuralgia at a stable dose during the study.
• Unable to refrain from excessive use of sedatives.

Sponsors & Collaborators

• Biogen: lead

Study Sites (1)

Professor Joanna Zakrzewska

London, United Kingdom

Location

Related Publications (3)

• Zakrzewska JM, Palmer J, Ettlin DA, Obermann M, Giblin GM, Morisset V, Tate S, Gunn K. Novel design for a phase IIa placebo-controlled, double-blind randomized withdrawal study to evaluate the safety and efficacy of CNV1014802 in patients with trigeminal neuralgia. Trials. 2013 Nov 23;14:402. doi: 10.1186/1745-6215-14-402.

  PMID: 24267010 BACKGROUND

• Zakrzewska JM, Palmer J, Bendtsen L, Di Stefano G, Ettlin DA, Maarbjerg S, Obermann M, Morisset V, Steiner D, Tate S, Cruccu G. Challenges recruiting to a proof-of-concept pharmaceutical trial for a rare disease: the trigeminal neuralgia experience. Trials. 2018 Dec 27;19(1):704. doi: 10.1186/s13063-018-3045-1.

  PMID: 30587219 DERIVED

• Zakrzewska JM, Palmer J, Morisset V, Giblin GM, Obermann M, Ettlin DA, Cruccu G, Bendtsen L, Estacion M, Derjean D, Waxman SG, Layton G, Gunn K, Tate S; study investigators. Safety and efficacy of a Nav1.7 selective sodium channel blocker in patients with trigeminal neuralgia: a double-blind, placebo-controlled, randomised withdrawal phase 2a trial. Lancet Neurol. 2017 Apr;16(4):291-300. doi: 10.1016/S1474-4422(17)30005-4. Epub 2017 Feb 17.

  PMID: 28216232 DERIVED

Related Links

• EudraCT Tabulated Result

MeSH Terms

Conditions

Trigeminal Neuralgia

Interventions

vixotrigine

Condition Hierarchy (Ancestors)

Trigeminal Nerve Diseases; Facial Neuralgia; Facial Nerve Diseases; Mouth Diseases; Stomatognathic Diseases; Cranial Nerve Diseases; Nervous System Diseases

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2012
• First Posted: February 29, 2012
• Study Start: March 31, 2012
• Primary Completion: March 31, 2014
• Study Completion: June 30, 2014
• Last Updated: January 10, 2019

Record last verified: 2019-01

Locations

GB (1)