A Phase 1, Open-label, 2-cohort, Fixed-sequence, Drug-drug Interaction Study to Investigate the Potential Interaction Between ATI-2173 When Coadministered With Midazolam or Clarithromycin in Healthy Subjects
Overview
- Phase
- Phase 1
- Intervention
- ATI-2173
- Conditions
- Drug Drug Interaction
- Sponsor
- Antios Therapeutics, Inc
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Cmax of Midazolam
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
ATI-2173 50 mg
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
Intervention: ATI-2173
Midazolam
Midazolam is a sensitive CYP3A index substrate
Intervention: Midazolam
Clarithromycin
Clarithromycin is a sensitive P-gp index inhibitor to evaluate potential effect of P-gp inhibition on ATI-2173 and its metabolites
Intervention: Clarithromycin
Outcomes
Primary Outcomes
Cmax of Midazolam
Time Frame: Through end of study, approximately 3 months
AUC0-t of Midazolam
Time Frame: Through end of study, approximately 3 months
AUC0-inf of Midazolam
Time Frame: Through end of study, approximately 3 months
Cmax of ATI-2173
Time Frame: Through end of study, approximately 3 months
AUCtau of ATI-2173
Time Frame: Through end of study, approximately 3 months
AUC0-t of ATI-2173
Time Frame: Through end of study, approximately 3 months
AUCo-inf of ATI-2173
Time Frame: Through end of study, approximately 3 months
Secondary Outcomes
- Number of adverse events(Through end of study, approximately 3 months)