An Evaluation of The Absolute Bioavailability of TH104

This is a single-dose, single-center, open-label, randomized, 2-way crossover study (2 treatments, 2 periods and 2 sequences) of a buccal formulation of Nalmefene 16 mg and a 1 mg intravenous dose of nalmefene injection, with a least 7 days washout period between doses.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Nalmefene

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nevada
    • Las Vegas, Nevada, United States, 89121
      • Novum Pharmaceutical Research Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Subject age between 18 to 55 years old.
2. Subject body weight ≤ 120 kg, with a BMI within of 18-30 kg/m2
3. Subject is able to complete the clinical study including the follow-up.
4. Subject is capable of providing written informed consent.

Exclusion Criteria:

1. Breastfeeding female.
2. Positive pregnancy test (female).
3. Systolic blood pressure outside 80-140 mm Hg or diastolic blood pressure outside 50-80 mm Hg.
4. Bradycardia defined as symptomatic heart rate < 60 bpm or asymptomatic heart rate < 55 bpm and tachycardia defined as resting heart rate > 100 bpm.
5. Clinically significant ECG abnormalities.
6. QTc > 450 ms for male and > 460 ms for female.
7. A history of allergies, or any significant adverse reactions, to any medications.
8. A history of seizures or convulsions.
9. Clinically significant medical, familial, or surgical history of eyes, ears, nose, throat, respiratory, cardiovascular, gastrointestinal, genitourinary, neurological, hematopoietic, lymphatic, endocrine, metabolic, dermatological, musculoskeletal, psychological and/or other major disease or malignancy.
10. Family history of sudden cardiac death.
11. Clinically significant physical examination finding.
12. Clinically significant laboratory abnormalities.
13. Hemoglobin < 12.0 g/dL for male and < 11.0 g/dL for female at screening.
14. Creatinine clearance <90 mL/m2/min
15. Total bilirubin , ALT/AST greater than upper limit of normal, or CPK > 2 x upper limit of normal.
16. Hepatitis B, Hepatitis C or HIV positive.
17. Positive test for drugs of abuse.
18. Smoke more than 10 sticks of cigarettes a day, vape more than 20 mg of liquid nicotine a day, or equivalent.
19. A history of drug or substance abuse, including alcohol (≥ 7 units per week) within 6 months before dosing (1 unit of alcohol equals approximately ½ pint [240 mL] of beer, 1 glass [125 mL] of wine, or 1 shot [25 mL] of spirit).
20. Have taken any medications (including herbal remedies) within 7 days before dosing, with the exception of birth control medications and other medications deemed acceptable by the Investigator.
21. Use of any opioid antagonist (e.g., naloxone, naltrexone, nalmefene) in the past.
22. Clinically significant illness or injury or hospitalization for any reason within 28 days before dosing.
23. Participation in other clinical study involving a marketed or investigational drug within 28 days or 10 half-lives of the drug before dosing, whichever is longer.

24. Donation of > 500 mL of plasma within 14 days before dosing; or donation or loss of whole blood (excluding the amount of blood collected during screening) before dosing as follows:

    • 50-300 mL within 28 days,
    • 301-500 mL within 42 days, or
    • 500 mL within 84 days.
25. Any other medical condition or reason that, in the opinion of the Investigator or Research Physician, makes the subject unsuitable to participate in the clinical study.

26. Female of childbearing potential having unprotected sexual intercourse with any non-sterile male partner within 14 days before dosing and until 60 days after receiving the last dose; acceptable methods of contraception include:

    • double barrier (1 by each partner), and at least 1 of these barriers (condom, cervical cap, diaphragm or sponge) must contain spermicide,
    • hormonal (oral, injectable, transdermal, intravaginal or implantable),
    • intrauterine contraceptive system,
    • surgical (vasectomy or tubal ligation), or
    • sexual abstinence.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1; A buccal formulation of Nalmefene 16 mg and a 1 mg intravenous dose of nalmefene injection, with a least 7 days washout period between dose	Drug: Nalmefene; Opioid antagonist
Experimental: Sequence 2; A 1 mg intravenous dose of nalmefene injection, and a buccal formulation of Nalmefene 16 mg with a least 7 days washout period between dose	Drug: Nalmefene; Opioid antagonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration Versus Time Curve (AUC) of Nalmefene	Determine the absolute bioavailability of a buccal dose of TH104	4 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Related Adverse Events	To compare the tolerability of TH104 films with intravenous nalmefene	4 days

Collaborators and Investigators

• Sponsor: Tharimmune Inc

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2024
• Primary Completion (Actual): February 11, 2024
• Study Completion (Actual): November 6, 2024

Study Registration Dates

• First Submitted: December 27, 2023
• First Submitted That Met QC Criteria: December 27, 2023
• First Posted (Actual): January 10, 2024

Study Record Updates

• Last Update Posted (Actual): April 8, 2025
• Last Update Submitted That Met QC Criteria: April 4, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Nalmefene
• Other Study ID Numbers: TH104-105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No