A Drug-Drug Interaction Study Between ATI-2173 and Midazolam or Clarithromycin in Healthy Subjects

NCT05137600 | Completed Phase 1

• 1 other identifier: ANTT103
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-center, open-label, 2-cohort, fixed-sequence, DDI study in healthy adult subjects. Healthy volunteers will be administered multiple oral doses of ATI-2173 in combination with midazolam or clarithromycin 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 midazolam or clarithromycin.

Conditions

Drug Drug Interaction

Outcome Measures

Primary Outcomes (7)

• Cmax of Midazolam

  Through end of study, approximately 3 months

• AUC0-t of Midazolam

  Through end of study, approximately 3 months

• AUC0-inf of Midazolam

  Through end of study, approximately 3 months

• Cmax of ATI-2173

  Through end of study, approximately 3 months

• AUCtau of ATI-2173

  Through end of study, approximately 3 months

• AUC0-t of ATI-2173

  Through end of study, approximately 3 months

• AUCo-inf of ATI-2173

  Through end of study, approximately 3 months

Secondary Outcomes (1)

• Number of adverse events

  Through end of study, approximately 3 months

Other Outcomes (11)

• Cmax of 1-hydroxymidazolam

  Through end of study, approximately 3 months

• AUC0-t of 1-hydroxymidazolam

  Through end of study, approximately 3 months

• AUC0-inf of 1-hydroxymidazolam

  Through end of study, approximately 3 months

Study Arms (3)

ATI-2173 50 mg

EXPERIMENTAL

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

Drug: ATI-2173

Midazolam

EXPERIMENTAL

Midazolam is a sensitive CYP3A index substrate

Drug: Midazolam

Clarithromycin

EXPERIMENTAL

Clarithromycin is a sensitive P-gp index inhibitor to evaluate potential effect of P-gp inhibition on ATI-2173 and its metabolites

Drug: Clarithromycin

Interventions

ATI-2173 DRUG

ATI-2173 is a liver-targeted phosphoramidate 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 50 mg

Midazolam DRUG

Midazolam is a sensitive CYP3A index substrate

Midazolam

Clarithromycin DRUG

Clarithromycin is a sensitive P-gp index inhibitor to evaluate potential effect of P-gp inhibition on ATI-2173 and its metabolites(clarithromycin)

Clarithromycin

Eligibility Criteria

• Age: 18 Years - 60 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 60 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
• If female, meets 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 the first study drug administration through to at least 60 days after the last dose of the study drug
• Non-hormonal intrauterine device (IUD) with a barrier method (eg, male condom) used 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
• Double-barrier method (eg, male condom, spermicide and diaphragm or cervical cap used simultaneously )from Screening through to at least 60 days after the last dose of the study drug
• Male partner vasectomized at least 6 months prior to Screening Or
• Is of non-childbearing potential, defined as surgically sterile (ie, has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or is in a postmenopausal state (ie, at least 1 year without menses without an alternative medical condition prior to the first study drug administration), as confirmed by follicle-stimulating hormone levels (≥ 40 mIU/mL).
• If male, meets one of the following criteria:

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
• Female using the following systemic contraceptives: oral, patch or vaginal ring, in the 28 days prior to the first study drug administration
• Female using hormone replacement therapy in the 28 days prior to the first study drug administration
• Female using the following systemic contraceptives: injections or implant, or hormone-releasing IUD in the 13 weeks prior to the first study drug administration
• Seated 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
• Seated blood pressure below 105/60 mmHg or higher than 140/90 mmHg at Screening or prior to the first study drug administration
• Estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73m2, calculated using the Modification of Diet in Renal Disease (MDRD) equation, at Screening or prior to the first study drug administration
• Presence of out-of-range cardiac interval (PR \< 110 msec, PR \> 200 msec, QRS \< 60 msec, QRS \>110 msec and QTcF \> 440 msec) on the ECG at Screening or at Check-in or other clinically significant ECG abnormalities, unless deemed non-significant by an Investigator
• Hemoglobin value below the lower limit of the reference laboratory at Screening or prior to study drug administration
• Any other clinically significant abnormalities in laboratory test results at Screening. Subjects with alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatine kinase (CK) or total bilirubin outside the normal range at Screening or Day -1 will be excluded.
• Positive test result for alcohol and/or drugs of abuse at Screening or prior to the first drug administration
• Positive screening results to HIV Ag/Ab combo, hepatitis B surface antigen or hepatitis C virus antibody tests at Screening
• Positive screening results to SARS-CoV-2 virus tests prior to the first study drug administration
• History of significant hypersensitivity to ATI-2173, clevudine, midazolam, clarithromycin, or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs

Sponsors & Collaborators

• Antios Therapeutics, Inc: lead

Study Sites (1)

Altasciences

Montreal, Quebec, H3P 3P1, Canada

Location

MeSH Terms

Interventions

Midazolam; Clarithromycin

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

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 28, 2021
• First Posted: November 30, 2021
• Study Start: October 28, 2021
• Primary Completion: December 23, 2021
• Study Completion: January 23, 2022
• Last Updated: February 4, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)