Comparative Pharmacokinetics and Safety of 3 Different Formulations of TNX-102 2.8 mg SL Tablets and Cyclobenzaprine 5 mg Oral Tablet in Healthy Adults

• ClinicalTrials.gov Identifier: NCT01889173
• Recruitment Status: Completed
• First Posted: June 28, 2013
• Last Update Posted: September 26, 2014
• Sponsor: Tonix Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Tonix Pharmaceuticals, Inc.

Study Description

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 3 different formulations of TNX-102 2.8 mg SL Tablets (a new formulation of cyclobenzaprine designed to result in increased dosage precision and decreased potential for morning grogginess) and to compare the bio-availability of 3 different formulations of TNX-102 2.8 mg SL Tablets (TNX-102 with potassium phosphate, TNX-102-B with sodium phosphate, and TNX-102-C with trisodium citrate) to that of cyclobenzaprine (5 mg tablets).

Condition or disease	Intervention/treatment	Phase
Healthy Adults	Drug: TNX-102 SL Tablets at 2.8 mg; Drug: TNX-102-B SL Tablets at 2.8 mg; Drug: TNX-102-C SL Tablets at 2.8 mg; Drug: Cyclobenzaprine tablets	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single-Dose, Open-Label, Randomized, Parallel-Design Study Of The Comparative Pharmacokinetics And Safety Of TNX-102 2.8 mg SL Tablets (With Potassium Phosphate) At 2.8 mg, TNX-102-B 2.8 mg SL Tablets (With Sodium Phosphate) At 2.8 mg, TNX-102-C 2.8 mg SL Tablets (With Trisodium Citrate) At 2.8 mg, And Cyclobenzaprine 5 mg Oral Tablets In Healthy Adults
• Study Start Date: June 2013
• Actual Primary Completion Date: December 2013
• Actual Study Completion Date: March 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: TNX-102 SL Tablets at 2.8 mg; 1 x TNX-102 SL Tablets (with potassium phosphate) at 2.8 mg	Drug: TNX-102 SL Tablets at 2.8 mg; 1 x TNX-102 SL Tablet (with potassium phosphate) at 2.8 mg held under the tongue until dissolution, without swallowing or chewing it.
Experimental: TNX-102-B SL Tablets at 2.8 mg; 1 x TNX-102-B SL Tablets (with sodium phosphate) at 2.8 mg	Drug: TNX-102-B SL Tablets at 2.8 mg; 1 x TNX-102-B SL Tablet (with sodium phosphate) at 2.8 mg held under the tongue until dissolution, without swallowing or chewing it.
Experimental: TNX-102-C SL Tablets at 2.8 mg; 1 x TNX-102-C SL Tablets (with trisodium citrate) at 2.8 mg	Drug: TNX-102-C SL Tablets at 2.8 mg; 1 x TNX-102-C SL Tablet (with trisodium citrate) at 2.8 mg held under the tongue until dissolution, without swallowing or chewing it.
Active Comparator: Cyclobenzaprine tablets; 1 x 5 mg cyclobenzaprine oral tablet	Drug: Cyclobenzaprine tablets; 1 x 5 mg cyclobenzaprine tablet, swallowed with 240 mL of room-temperature water

Outcome Measures

Primary Outcome Measures :

1. Measured levels of cyclobenzaprine and norcyclobenzaprine in plasma and urine [ Time Frame: 26 time points per period for blood assessment ; 2 pooled analyses in 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, and 48 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 and 24-48 hours post-dose.
2. Safety and tolerability of the 3 formulations of TNX-102 SL Tablets at 2.8 mg [ Time Frame: Continuously until the end (day 3) of the study period + Telephone follow-up 7-13 days after dosing (total duration: about 1 month) ]
   Every adverse events occurring during the study period will be reported.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Healthy adults
• Male or female
• 18-65 years old
• Non-smoker
• BMI > 18.5 and < 30.0
• With medically acceptable form of contraception (female only)
• With signed informed consent

Exclusion Criteria:

• 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 (within 30 days), or of > 499 mL (within 56 days) prior to dosing.

Contacts and Locations

Locations

Canada, Quebec

PharmaNet, Inc.

Quebec City, Quebec, Canada, G1P 0A2

Sponsors and Collaborators

Tonix Pharmaceuticals, Inc.

Investigators

• Study Chair: Seth M. Lederman, MD; Tonix Pharmaceuticals, Inc.
• Study Director: Jeffrey P. Kitrelle, MD; Tonix Pharmaceuticals, Inc.
• Principal Investigator: Denis Audet, MD; PharmaNet

More Information

• Responsible Party: Tonix Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01889173 History of Changes
• Other Study ID Numbers: TNX-CY-F104
• First Posted: June 28, 2013
• Last Update Posted: September 26, 2014
• Last Verified: September 2014

Additional relevant MeSH terms:

Amitriptyline; Cyclobenzaprine; Citric Acid; Sodium Citrate; Potassium phosphate; Anticoagulants; Calcium Chelating Agents; Chelating Agents; Sequestering Agents; Molecular Mechanisms of Pharmacological Action; Antidepressive Agents, Tricyclic; Antidepressive Agents; Psychotropic Drugs; Muscle Relaxants, Central; Physiological Effects of Drugs; Neuromuscular Agents; Peripheral Nervous System Agents; Tranquilizing Agents; Central Nervous System Depressants; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Adrenergic Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Adrenergic Agents; Neurotransmitter Agents; Cariostatic Agents; Protective Agents