Comparative Bioavailability of Sublingual TNX-102, Oral and Intravenous Cyclobenzaprine in Healthy Adults

NCT01634412 | Completed Phase 1

• 1 other identifier: TNX-CY-F102
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Very low dose (VLD) cyclobenzaprine at bedtime has shown promise as a treatment for fibromyalgia, but the chemistry of cyclobenzaprine requires new formulation technology for bedtime use. The present trial is designed to assess the safety and tolerability of sublingual TNX-102 2.4 mg (a new formulation of cyclobenzaprine designed to result in increased dosage precision and decreased potential for morning grogginess) at pH 3.5 and 7.1 and to compare the bio-availability of sublingual TNX-102 2.4 mg at pH 3.5 and 7.1 and cyclobenzaprine (5 mg tablets, or 2.4 mg iv).

Conditions

Healthy Adults

Outcome Measures

Primary Outcomes (2)

• • Measured levels of cyclobenzaprine and norcyclobenzaprine in plasma and urine

  Blood samples will be taken per period: within 30 minutes pre-dose and 2, 3.5, 5, 10, 20, 30, and 45 minutes and 1, 2, 2.5, 3, 3.33, 3.67, 4, 4.33, 4.67, 5, 5.5, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose. A single urine sample will be collected within 30 minutes pre-dose (one sample), and urine will be pooled from 0-24, 24-48 and 48-72 hours post-dose.

  27 time points per period for blood assessment ; 3 pooled analyses in urine.

• Safety and tolerability of sublingual TNX-102 2.4 mg at pH 3.5 and pH 7.1.

  Every adverse events occurring during the study period will be reported.

  Continuously until the end (day 4) of the study period + Telephone follow-up 7-13 days after dosing (total duration: about 1 month)

Study Arms (4)

SL TNX-102 at pH 3.5

EXPERIMENTAL

2.4 mg TNX-102 sublingual solution (2.4 mg/mL) in PBS at pH 3.5

Drug: SL TNX-102 2.4 mg at pH 3.5

SL TNX-102 at pH 7.1

EXPERIMENTAL

2.4 mg TNX-102 sublingual solution (2.4 mg/mL) in PBS at pH 7.1

Drug: SL TNX-102 2.4 mg at pH 7.1

Cyclobenzaprine tablets

ACTIVE COMPARATOR

5 mg cyclobenzaprine tablet once

Drug: Cyclobenzaprine Tablet

Cyclobenzaprine IV

ACTIVE COMPARATOR

2.4 mg cyclobenzaprine USP in PBS (0.6 mg/mL) at pH 7.4

Drug: Cyclobenzaprine IV

Interventions

SL TNX-102 2.4 mg at pH 3.5 DRUG

1 dose of 2.4 mg TNX-102 sublingual solution (2.4 mg/mL) in PBS at pH 3.5, administered as 1 mL held under the tongue for 90 seconds without swallowing

SL TNX-102 at pH 3.5

SL TNX-102 2.4 mg at pH 7.1 DRUG

1 dose of 2.4 mg TNX-102 sublingual solution (2.4 mg/mL) in PBS at pH 7.1, administered as 1 mL held under the tongue for 90 seconds without swallowing

SL TNX-102 at pH 7.1

Cyclobenzaprine Tablet DRUG

1 x 5 mg cyclobenzaprine tablet, swallowed with 240 mL of room-temperature water

Cyclobenzaprine tablets

Cyclobenzaprine IV DRUG

1 dose of 2.4 mg cyclobenzaprine USP in PBS (0.6 mg/mL) at pH 7.4, administered intravenously as a 4 mL bolus injection over 30 seconds

Cyclobenzaprine IV

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female
• Non-smoker
• years old
• BMI \> 18.5 and \< 30.0
• With medically acceptable form of contraception (female only)
• With signed informed consent

You may not qualify if:

• Any clinically significant abnormality including ECG abnormalities or vital sign abnormalities (systolic blood pressure \< 90 or \> 140 mmHg, diastolic blood pressure lower \< 50 or \> 90 mmHg, or heart rate \< 50 or \> 100 BPM)
• Any abnormal laboratory test (including positivity for Hep B, Hep C, HIV, and Hemoglobin \< 128 g/L (males) or \< 115 g/L (females) and hematocrit \< 0.37 L/L (males) or \< 0.32 L/L (females))
• History of alcohol or drug abuse or dependence within 1 year and/or positive drug, cotinine, or alcohol tests
• Use of any drug (within 30 days), supplement, or food (within 14 days) known to induce or inhibit hepatic drug metabolism prior to study medication
• Positive pregnancy test, breastfeeding or lactating
• Use of medication other than hormonal contraceptives or topical products, including OTC, natural health products, MAO inhibitors
• Participation in an investigational study within 30 days prior to dosing
• Donation of plasma (within 7 days), or donation or loss of blood of 50-499 mL (within30 days), or of \> 499 mL (within 56 days) prior to dosing.

Sponsors & Collaborators

• Tonix Pharmaceuticals, Inc.: lead

Study Sites (1)

PharmaNet, Inc.

Québec, Quebec, G1P 0A2, Canada

Location

MeSH Terms

Interventions

cyclobenzaprine

Study Officials

• Seth M. Lederman, MD

  Tonix Pharmaceuticals, Inc.

  STUDY CHAIR

• Jeffrey P. Kitrelle, MD

  Tonix Pharmaceuticals, Inc.

  STUDY DIRECTOR

• Denis Audet, MD

  PharmaNet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2012
• First Posted: July 6, 2012
• Study Start: June 1, 2012
• Primary Completion: September 1, 2013
• Study Completion: January 1, 2014
• Last Updated: September 26, 2014

Record last verified: 2014-09

Locations

CA (1)