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The Effect of Lacosamide in Peripheral Neuropathic Pain

Primary Purpose

Neuropathic Pain, Neuropathy;Peripheral, Neuropathy, Painful

Status

Terminated

Phase

Phase 2

Locations

Denmark

Study Type

Interventional

Intervention

Lacosamide

Placebo

About this trial

This is an interventional treatment trial for Neuropathic Pain

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Sites / Locations

Danish Pain Research Center, Aarhus University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Lacosamide

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Pain relief

(complete, good, moderate, mild, none, worse pain) . Measured at last visit/end of treatment period.

Use of escape medicine (paracetamol) during treatment period.

Number of paracetamol tablets during the 12 weeks treatment period.

Full Information

NCT ID

NCT03777956

First Posted

December 14, 2018

Last Updated

February 15, 2023

Sponsor

Danish Pain Research Center

Collaborators

Odense University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03777956

Brief Title

The Effect of Lacosamide in Peripheral Neuropathic Pain

Official Title

The Effect of Lacosamide in Peripheral Neuropathic Pain: a Randomized, Double-blind, Placebo Controlled, Phenotype-stratified Study

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Terminated

Why Stopped

COVID 19 and recruitment problems

Study Start Date

January 15, 2019 (Actual)

Primary Completion Date

June 3, 2022 (Actual)

Study Completion Date

June 3, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Danish Pain Research Center

Collaborators

Odense University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Detailed Description

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. As this is a mechanistic study, the main purpose is to compare the change in pain intensity in patients who receive an expected sufficiently effective dose of lacosamide. As supportive evidence for a drug-specific predictive biomarker, the purpose is also to compare the change in pain intensity during lacosamide vs. placebo for the two phenotypes. We hypothesize that the sodium-channel blocker lacosamide will be more effective in patients with the irritable nociceptor than those without the non-irritable nociceptor phenotype, and that lacosamide is more effective than placebo in patients with the irritable nociceptor phenotype.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

63 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Lacosamide

Arm Type

Active Comparator

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Lacosamide

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

Pain intensity

Description

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

Pain relief

Description

(complete, good, moderate, mild, none, worse pain) . Measured at last visit/end of treatment period.

Time Frame

12 weeks

Title

Use of escape medicine (paracetamol) during treatment period.

Description

Number of paracetamol tablets during the 12 weeks treatment period.

Time Frame

12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nanna B Finnerup, Professor

Organizational Affiliation

Danish Pain Research Center

Official's Role

Study Director

Facility Information:

Facility Name

Danish Pain Research Center, Aarhus University Hospital

City

Aarhus

ZIP/Postal Code

8200

Country

Denmark

12. IPD Sharing Statement

Citations:

PubMed Identifier

27115670

Citation

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.

Results Reference

background

PubMed Identifier

22494920

Citation

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.

Results Reference

background

PubMed Identifier

31604475

Citation

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.

Results Reference

derived

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The Effect of Lacosamide in Peripheral Neuropathic Pain

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