Safety and Tolerability of Lacosamide in Patients With Gain-of-function Nav1.7 Mutations Related Small Fiber Neuropathy

• Status: Completed
• Trial end date: 2017-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Lacosamide is a functionalized amino acid with antinociceptive properties in inflammatory and neuropathic pain, and displays a unique mechanism: it enhances slow inactivation of Nav1.3, Nav1.7, and Nav1.8.

Nav1.7 is expressed predominantly in nociceptive and sympathetic neurons. Gain-of-function mutations have been described in Nav1.7 that result in extreme pain disorders such as SCN9A-associated small fiber neuropathy. In the disease states genetically linked to a gain-of-function of Nav1.7, the sodium channel is mutated to increase the sodium influx resulting in a hyperexcitable sensory neuron, and a resultant sensation of pain.

The objective of the study is to determine the efficacy and safety of lacosamide, a sodium channel blocker, in patients with pain due to SCN9A-associated small fiber neuropathy.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Academisch Ziekenhuis Maastricht
• Treatments: Lacosamide

Criteria

Inclusion Criteria:

1. Male and/or female subjects between the ages of 18 and 80 years.

2. Presence of a clinical diagnosis of Small Fiber Neuropathy (SFN), 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.

Exclusion Criteria:

1. Subjects with predominantly signs of large nerve fiber involvement, clinically significant abnormal nerve conduction studies.

2. History or presence of illnesses known to cause SFN (excluding diabetes mellitus).

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.

5. History of known alcohol, analgesic or illicit drug abuse within 12 months of Screening.

6. Subjects taking medications with activity at sodium channels. 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 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.

13. In the case of incidental findings the patient and his/her treating physician will be informed and asked to undertake action if necessary. If a patient does not want to be informed about possible incidental findings, nor wants his treating physician to be informed, he or she cannot participate in this study.