The Effect of Lacosamide in Peripheral Neuropathic Pain

NCT03777956 | Terminated Phase 2 DMC

• 2 other identifiers: LACOSAMIDE-20182018-003110-40
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to compare the change in pain intensity during treatment with a sodium-channel blocker (lacosamide) in patients with peripheral neuropathic pain with and without the irritable nociceptor phenotype.

Conditions

Neuropathic Pain; Neuropathy;Peripheral; Neuropathy, Painful; Neuropathy, Diabetic; Neuropathy

Outcome Measures

Primary Outcomes (1)

• Pain intensity

  The difference in the mean value of the patient's daily ratings of average pain intensity in the baseline week and the last week during treatment as experienced during the past 24 hours rated on a 0-10 point numeric rating scale (NRS; 0 = no pain, 10 = worst possible pain). The primary objective is to compare the change in pain intensity from baseline to last week of lacosamide treatment in patients with and without the irritable nociceptor phenotype in the PP population. The supportive objective is to compare the effect of lacosamide vs. placebo in the two phenotype groups in the PP population. Although we do not expect a phenotype difference in the response to placebo, a comparison of the effect of lacosamide vs. placebo is needed to justify that the phenotype is a predictive biomarker for the effect of lacosamide.

  12 weeks

Secondary Outcomes (2)

• Pain relief

  12 weeks

• Use of escape medicine (paracetamol) during treatment period.

  12 weeks

Study Arms (2)

Lacosamide

ACTIVE COMPARATOR

Lacosamide (50 mg) are given as capsules and taken orally twice a day, up to 200 mg b.i.d.

Drug: Lacosamide

Placebo

PLACEBO COMPARATOR

Placebo are given as capsules, same as lacosamide, and taken orally twice a day, without active ingredient.

Drug: Placebo

Interventions

Lacosamide DRUG

Lacosamide (50 mg) and identical placebo are given as capsules and taken orally twice a day, up to 200 mg b.i.d.

Lacosamide

Placebo DRUG

Identical placebo are given as capsules and taken orally twice a day.

Placebo

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years.
• Probable or definite peripheral neuropathic pain for at least 3 months (Finnerup et al. 2016)
• Average pain intensity of at least 4 and not above 9 on a 0-10 NRS during the 7-day baseline week (Dworkin et al. 2012).
• Written informed consent.

You may not qualify if:

• Other causes of pain in the same area, or other concomitant pain that cannot be distinguished from the neuropathic pain
• Patient who cannot cooperate or are unable to complete the project and patients who do not speak Danish.
• Known and current cardiac conduction disturbance (2⁰ or 3⁰ atrioventricular (AV) block, prolonged QTc interval \> 450 ms, heart rate \<50 or \>110 bpm, a QRS interval \>120ms (ECG required)), significant cardiac, renal or liver disease or other severe illness. In patients treated with pregabalin also PQ interval \> 0,2s and cardiac disease. Sitting diastolic blood pressure below 50 mmHg or above 105 mmHg.
• Major depressive episode within 6 months, recurrent depressive disorder or other significant psychiatric disease, alcohol, illicit drug or drug abuse.
• Pregnancy or lactation
• Woman of childbearing potential, unless they use and acceptable effective contraception measure as defined in the Clinical Trials Facilitation Group (CTFG) during the study and at least 2 weeks after, or if their male partner is vasectomized and their sole partners. Negative pregnancy test is required.
• Known allergy to lacosamide or excipients.
• Concomitant pain treatment with tricyclic antidepressants, topical analgesics (lidocaine, capsaicin), lamotrigine, oxcarbazepine, cannabinoids or strong opioids that cannot be discontinued. Other treatment for neuropathic pain are allowed in a stable dose (from 14 days before randomization to completion of the trial), if they cannot be tapered off completely.
• Concomitant treatment with products known to be associated with PQ (PR) prolongation other than pregabalin.
• Patients inappropriate for placebo
• Planned surgery
• Use of sodium channel blockers within at least five half-lives and investigational drugs within 30 days.
• Patients on controlled sodium diet, unless the amount of sodium in the capsules is acceptable for their diet.
• The score "yes" on item 4 or item 5 of the Suicidal Ideation section of the Columbia Suicide Severity Rating Scale (C-SSRS), if the ideation occurred in the past 6 months, or "yes on any item of the Suicidal Behaviour section, except for the "Non-suicidal Self Injurious Behaviour" if this behaviour occurred in the past 2 years.

Sponsors & Collaborators

• Danish Pain Research Center: lead
• Odense University Hospital: collaborator

Study Sites (1)

Danish Pain Research Center, Aarhus University Hospital

Aarhus, 8200, Denmark

Location

Related Publications (3)

• Finnerup NB, Haroutounian S, Kamerman P, Baron R, Bennett DLH, Bouhassira D, Cruccu G, Freeman R, Hansson P, Nurmikko T, Raja SN, Rice ASC, Serra J, Smith BH, Treede RD, Jensen TS. Neuropathic pain: an updated grading system for research and clinical practice. Pain. 2016 Aug;157(8):1599-1606. doi: 10.1097/j.pain.0000000000000492.

  PMID: 27115670 BACKGROUND

• Dworkin RH, Turk DC, Peirce-Sandner S, Burke LB, Farrar JT, Gilron I, Jensen MP, Katz NP, Raja SN, Rappaport BA, Rowbotham MC, Backonja MM, Baron R, Bellamy N, Bhagwagar Z, Costello A, Cowan P, Fang WC, Hertz S, Jay GW, Junor R, Kerns RD, Kerwin R, Kopecky EA, Lissin D, Malamut R, Markman JD, McDermott MP, Munera C, Porter L, Rauschkolb C, Rice ASC, Sampaio C, Skljarevski V, Sommerville K, Stacey BR, Steigerwald I, Tobias J, Trentacosti AM, Wasan AD, Wells GA, Williams J, Witter J, Ziegler D. Considerations for improving assay sensitivity in chronic pain clinical trials: IMMPACT recommendations. Pain. 2012 Jun;153(6):1148-1158. doi: 10.1016/j.pain.2012.03.003. Epub 2012 Apr 9.

  PMID: 22494920 BACKGROUND

• Carmland ME, Kreutzfeldt M, Holbech JV, Andersen NT, Jensen TS, Bach FW, Sindrup SH, Finnerup NB. Effect of lacosamide in peripheral neuropathic pain: study protocol for a randomized, placebo-controlled, phenotype-stratified trial. Trials. 2019 Oct 11;20(1):588. doi: 10.1186/s13063-019-3695-7.

  PMID: 31604475 DERIVED

MeSH Terms

Conditions

Neuralgia; Neuritis; Neuropathy, Painful; Diabetic Neuropathies

Interventions

Lacosamide

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids

Study Officials

• Nanna B Finnerup, Professor

  Danish Pain Research Center

  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: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2018
• First Posted: December 19, 2018
• Study Start: January 15, 2019
• Primary Completion: June 3, 2022
• Study Completion: June 3, 2022
• Last Updated: February 16, 2023

Record last verified: 2023-02

Locations

DK (1)