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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| Midazolam | Experimental | Midazolam is a sensitive CYP3A index substrate |
|
| Clarithromycin | Experimental | Clarithromycin is a sensitive P-gp index inhibitor to evaluate potential effect of P-gp inhibition on ATI-2173 and its metabolites |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of adverse events | Through end of study, approximately 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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
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:
Is able to procreate and agrees to use one of the accepted contraceptive regimens and not to donate sperm from the first study drug administration to at least 90 days after the last drug administration. An acceptable method of contraception includes one of the following:
Is unable to procreate; defined as surgically sterile (ie, has undergone a vasectomy at least 6 months prior to Screening)
Agrees to abstain from blood or plasma donation from the Screening visit until 3 months after the last study drug administration
Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on the physical examination, vital signs, myopathy questionnaire, and/or ECG, as determined by an Investigator Cohort 1 only
Have no clinically significant findings on the neurological examination and/or oxygen saturation measurement as determined by an Investigator
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Altasciences | Montreal | Quebec | H3P 3P1 | Canada |
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| ID | Term |
|---|---|
| D008874 | Midazolam |
| D017291 | Clarithromycin |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| Midazolam | Drug | Midazolam is a sensitive CYP3A index substrate |
|
| 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) |
|
| Through end of study, approximately 3 months |
| Ratio of metabolite to parent (midazolam) for AUC0-t | Through end of study, approximately 3 months |
| Ratio of metabolite to parent (ATI-2173) for AUC0-t | Through end of study, approximately 3 months |
| Ratio of metabolite to parent (ATI-2173) for AUCtau | Through end of study, approximately 3 months |
| Cmax of M1 | Through end of study, approximately 3 months |
| AUC0-t of M1 | Through end of study, approximately 3 months |
| AUC0-inf of M1 | Through end of study, approximately 3 months |
| Cmax of clevudine | Through end of study, approximately 3 months |
| AUCtau of clevudine | Through end of study, approximately 3 months |
| D006571 | Heterocyclic Compounds |
| D004917 | Erythromycin |
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |