Efficacy, safety and tolerability of lacosamide in patients with small fiber neuropathy with a mutation in sodiumchannel 1.7: a randomized, double-blind, placebo controlled, crossover trial

Phase 1

• Conditions: SCN9A mutation related small fiber neuropathy; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2013-001511-70-NL
• Lead Sponsor: Maastricht University Medical Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-09-06
• Last Update Posted: 2 October 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1.Male and/or female subjects between the ages of 18 and 78 years.
2.Presence of a clinical diagnosis of Small Fiber Neuropathy (SFN) for at least 3 months prior to Screening, with at least 2 of the following clinical symptoms:
•Burning feet.
•Allodynia.
•Diminished pain and/or temperature sensation.
•Dry eyes or mouth.
•Orthostatic dizziness.
•Bowel disturbances (constipation, diarrhea, gastroparesis).
•Urinary disturbances.
•Sweat changes (hyper-/hypohidrosis).
•Visual accommodation problems and/or blurred vision.
•Hot flashes/palpitations.
•Impotence, diminished ejaculation or lubrication.
3.In addition to the clinical diagnosis of SFN, presence of confirmed abnormality on intra-epidermal nerve fiber density evaluation (IENFD) and/or Quantitative Sensory Testing (QST) and a mutation in the SCN9A gene, confirmed by sequencing. Where possible, in vitro confirmation of the functionality of the mutation should have been performed and documented.
4.Presence of pain due to SFN for at least 3 months prior to Screening and an average self-reported pain score of at least 3 during this time.
5.If on analgesic medication to manage pain due to SFN, subject must have stable analgesic medication for a minimum of 30 days prior to the start of the study and should continue with the same regimen throughout the study.
6.Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
7.Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

1.Subjects with predominantly signs of large nerve fiber involvement (muscle weakness, loss of vibration sense, hypo-/-areflexia), clinically significant abnormal nerve conduction studies (NCS).
2.History or presence of illnesses known to cause SFN (excluding diabetes mellitus), including liver, kidney or thyroid dysfunction, monoclonal gammopathy, connective tissue disorders, sarcoidosis, Sjogren syndrome, amyloidosis, Fabry disease, celiac disease, HIV and neurotoxic drugs (e.g., chemotherapy).
3.Subjects with other severe pain conditions which may impair the self-assessment of pain due to SFN.
4.Any condition possibly affecting drug intake and absorption (e.g., difficulty in swallowing, gastrectomy and /or bowel resection).
5.History of known alcohol, analgesic or illicit drug abuse within 12 months of Screening.
6.Subjects taking medications with activity at sodium channels e.g., lamotrigine, carbamazapine, oxcarbazapine, mexiletine, amitriptyline, topical analgesics e.g., lidocaine patches, capsaicin patches and oral/injectable corticosteroids. These medications are prohibited until the end of the study period and require a washout period of at least 5 half lives (90 days for capsaicin patches) prior to the Screening visit.
7.12-lead ECG demonstrating QTcF (Fridericia’s correction) >450 or a QRS interval >120 msec at Screening. If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTcF values should be used to determine the subject’s eligibility.
8.Severe renal impairment (creatinine clearance = 30 mL/min).
9.Treatment with an investigational drug within 30 days (or as determined by the local requirement, whichever is longer) or 5 half-lives preceding the first dose of study medication.
10.Participation in other studies during the period of current study participation, or has planned surgery during the course of the study.
11.Pregnant females; breastfeeding females; females of childbearing potential not using effective contraception or not agreeing to continue effective contraception for at least 28 days after the last dose of investigational product.
12.Other clinically significant or unstable, or severe acute or chronic medical or psychiatric/psychological condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified