A Drug-Drug Interaction Study Between ATI-2173 and Tenofovir Disoproxil Fumarate in Healthy Subjects

NCT05137548 | Completed Phase 1

• 1 other identifier: ANTT102
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-center, open-label, 2-cohort, multiple dose, fixed-sequence, DDI study in healthy adult subjects. Healthy volunteers will be administered multiple oral doses of ATI-2173 in combination with tenofovir disoproxil fumarate and assessed for safety and tolerability including blood tests to show how the body metabolizes and eliminates the investigational drug as well as how the investigational drug interacts with tenofovir disoproxil fumarate.

Conditions

Drug Interaction

Outcome Measures

Primary Outcomes (7)

• Cmax of ATI-2173, clevudine, and M1 in plasma

  Through end of study, approximately 3 months

• AUCtau of ATI-2173, clevudine, and M1 in plasma

  Through end of study, approximately 3 months

• AUC0-t of ATI-2173, clevudine, and M1 in plasma

  Through end of study, approximately 3 months

• Cmax of tenofovir

  Through end of study, approximately 3 months

• Cmin,ss of tenofovir

  Through end of study, approximately 3 months

• AUC0-tau of tenofovir

  Through end of study, approximately 3 months

• AUC0-t of tenofovir

  Through end of study, approximately 3 months

Secondary Outcomes (1)

• Number of Adverse Events

  Through end of study, approximately 3 months

Other Outcomes (1)

• Plasma trough concentrations of tenofovir, ATI-2173, clevudine, and M1

  Days 18, 19, 20 and 21

Study Arms (2)

ATI-2173.

EXPERIMENTAL

ATI-2173

Drug: ATI-2173 50 mg

Tenofovir Disoproxil Fumarate

EXPERIMENTAL

Tenofovir disoproxil fumarate

Drug: Tenofovir 300Mg Oral Tablet

Interventions

ATI-2173 50 mg DRUG

ATI-2173 is a liver-targeted phosphoramidate oral prodrug of clevudine designed to enhance anti-HBV activity while decreasing systemic exposure to clevudine. It will be dosed as a capsule by mouth

ATI-2173.

Tenofovir 300Mg Oral Tablet DRUG

Tenofovir is an oral nucleotide analogue reverse transcriptase inhibitor used for chronic hepatitis B virus. It will be dosed as a tablet by mouth

Also known as: Viread 300 mg

Tenofovir Disoproxil Fumarate

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated Informed Consent Form (ICF)
• Stated willingness to comply with all study procedures (including ability and willingness to abstain from alcohol from 48 hours prior to the first study drug administration until discharge) and availability for the duration of the study
• Healthy adult male or female
• Aged between 18 and 59 years, inclusive
• Body mass index (BMI) within 18.5 kg/m2 to 30.0 kg/m2, inclusively
• Non- or ex-smoker (an ex-smoker is defined as someone who completely stopped using nicotine products for at least 180 days prior to the first study drug administration)
• Suitable veins for cannulation or repeated venipuncture as assessed by an Investigator at Screening Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on the physical examination (including vital signs) and/or ECG, as determined by an Investigator
• \. Agrees to abstain from blood or plasma donation from the Screening visit until 3 months after the last study drug administration 10. If female, must meet one of the following criteria:
• Is of childbearing potential and agrees to use an acceptable contraceptive method. Acceptable contraceptive methods include:
• Abstinence from heterosexual intercourse from Screening through to at least 60 days after the last dose of the study drug
• Male partner vasectomized at least 180 days prior to Screening
• Double-barrier method (eg, male condom, spermicide and diaphragm or cervical cap used simultaneously) from Screening through to at least 30 days after the last dose of the study drug
• One of the following contraceptive methods with a barrier method (eg, male condom) from at least 28 days prior to the first study drug administration through to at least 60 days after the last dose of the study drug:
• Systemic contraceptives (combined birth control pills, injectable/implant/insertable hormonal birth control products, transdermal patch)
• Intrauterine device (with or without hormones) If systemic contraceptives are used, must agree to use an additional acceptable non-hormonal method during the study and for at least 60 days after the last dose of the study drug Or

You may not qualify if:

• Female who is lactating
• Female who is pregnant according to the pregnancy test at Screening or prior to the first study drug administration
• Pulse rate less than 50 beats per minute or more than 100 beats per minute at Screening or prior to the first study drug administration unless deemed not clinically significant by the Investigator
• Blood pressure below 100/60 mmHg or higher than 140/90 mmHg at Screening or prior to the first study drug administration unless deemed not clinically significant by the Investigator
• History of hypersensitivity to ATI-2173, clevudine, tenofovir, or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs
• Presence or history of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability including but not limited to cholecystectomy
• History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease, in the opinion of an Investigator
• Presence of clinically significant ECG abnormalities at Screening or prior to study drug administration, in the opinion of an Investigator
• Presence of clinically significant muscle disorders, myopathies or other forms of liver disease, in the opinion of an Investigator
• Estimated glomerular filtration rate (eGFR) \< 80 mL/min/1.73 m2 using the Modification of Diet in Renal Disease (MDRD) equation at Screening or \< 60 mL/min/1.73 m2 on Day -1
• Hemoglobin value below the lower limit of the reference laboratory at Screening or prior to study drug administration
• Unexplained persistent elevations of serum transaminases or creatine kinase (CK) levels at Screening or prior to study drug administration
• Maintenance therapy with any drug or significant history of drug dependency or alcohol abuse (\> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
• Any clinically significant illness in the 28 days prior to the first study drug administration
• Use of any prescription drugs (except systemic contraception and intrauterine devices) in the 30 days prior to the first study drug administration, that in the opinion of an Investigator would put into question the status of the participant as healthy

Sponsors & Collaborators

• Antios Therapeutics, Inc: lead

Study Sites (1)

Altasciences

Montreal, Quebec, H3P 3P1, Canada

Location

MeSH Terms

Interventions

Tenofovir; Tablets

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Study Design

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

Study Record Dates

• First Submitted: October 27, 2021
• First Posted: November 30, 2021
• Study Start: October 27, 2021
• Primary Completion: December 23, 2021
• Study Completion: December 23, 2021
• Last Updated: February 4, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)