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The purpose of this study is to compare the single-dose pharmacokinetics (PK) of two formulations (Formulation 1 and Formulation 2) of AG-881 and to examine the effect of food and multiple-dose omeprazole on the single-dose PK of AG-881 Formulation 2 in healthy adult participants. This study will also assess the safety and tolerability of single-dose AG-881 (Formulation 1 and 2) alone and of AG-881 Formulation 2 when administered with and without food and when coadministered with omeprazole in healthy adult subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment Sequence ABCD | Experimental | Participants will receive Treatment A (AG-881 Formulation 1, 50 mg, tablet orally, under fasted condition once on Day 1 of Period 1) followed by Treatment B (AG-881 Formulation 2, 50 mg, tablet orally, under fasted condition once on Day 1 of Period 2) followed by Treatment C (AG-881 Formulation 2, 50 mg, tablet, orally, under fed condition once on Day 1 of Period 3) followed by Treatment D (omeprazole 40 mg capsule, orally, once daily on Days 1 to 4 and AG-881 Formulation 2, 50 mg, tablet, orally, under fasted condition, once on Day 4 of Period 4). Each period will be separated by a Washout Period of 21 days. |
|
| Treatment Sequence BCAD | Experimental | Participants will receive Treatment B in Period 1 followed by Treatment C in Period 2 then Treatment A in Period 3 followed by Treatment D in Period 4. Each period will be separated by a Washout Period of 21 days. |
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| Treatment Sequence CABD | Experimental | Participants will receive Treatment C in Period 1 followed by Treatment A in Period 2 then Treatment B in Period 3 followed by Treatment D in Period 4. Each period will be separated by a Washout Period of 21 days. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AG881 Formulation 1 | Drug | AG881 uncoated tablets |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-Time Curve From Time 0 to the Last Observed Non-Zero Concentration (AUC0-t) of AG-881 Formulation 1 without Food | Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881 | |
| Area Under the Concentration-Time Curve From Time 0 to the Last Observed Non-Zero Concentration (AUC0-t) of AG-881 Formulation 2 with Food, without Food and when Co-administered with Omeprazole | Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881 | |
| Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of AG-881 Formulation 1 without Food | Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881 | |
| Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of AG-881 Formulation 2 with Food, without Food and when Co-administered with Omeprazole | Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881 | |
| Maximum Observed Concentration (Cmax) of AG-881 Formulation 1 without Food | Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881 | |
| Maximum Observed Concentration (Cmax) of AG-881 Formulation 2 with Food, without Food and when Co-administered with Omeprazole | Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881 | |
| Area Under the Concentration-Time Curve, From Time 0 to 504 Hours Postdose (AUC0-504) of AG-881 Formulation 1 without Food |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Abnormalities in Triplicate 12-lead Electrocardiograms (ECGs) | Up to 21 days in Period 1, 2, 3 (Each period is 21 days); up to 25 days in Period 4 (Period 4 is 25 days) | |
| Number of Participants with Abnormalities in Vital Sign Measurements |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Affairs | Agios Pharmaceuticals, Inc. | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Celerion | Tempe | Arizona | 85283 | United States |
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| AG881 Formulation 2 | Drug | AG881 film-coated tablets |
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| Omeprazole | Drug | Omeprazole capsules |
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| Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881 |
| Area Under the Concentration-Time Curve, From Time 0 to 504 Hours Postdose (AUC0-504) of AG-881 Formulation 2 with Food, without Food and when Co-administered with Omeprazole | Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881 |
| Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of AG-881 Formulation 1 without Food | Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881 |
| Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of AG-881 Formulation 2 with Food, without Food and when Co-administered with Omeprazole | Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881 |
| Apparent Terminal Elimination Half-life (t½) of AG-881 Formulation 1 without Food | Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881 |
| Apparent Terminal Elimination Half-life (t½) of AG-881 Formulation 2 with Food, without Food and when Co-administered with Omeprazole | Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881 |
| Time Delay Between Drug Administration and the Onset of Absorption (tlag) of AG-881 Formulation 1 without Food | Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881 |
| Time Delay Between Drug Administration and the Onset of Absorption (tlag) of AG-881 Formulation 2 with Food, without Food and when Co-administered with Omeprazole | Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881 |
| Time to Reach Maximum Observed Concentration (Tmax) of AG-881 Formulation 1 without Food | Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881 |
| Time to Reach Maximum Observed Concentration (Tmax) of AG-881 Formulation 2 with Food, without Food and when Co-administered with Omeprazole | Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881 |
| Apparent Volume of Distribution After Oral (Extravascular) Administration (Vd/F) of AG-881 Formulation 1 without Food | Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881 |
| Apparent Volume of Distribution After Oral (Extravascular) Administration (Vd/F) of AG-881 Formulation 2 with Food, without Food and when Co-administered with Omeprazole | Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881 |
Vital sign measurements will include body temperature, respiratory rate, blood pressure, and heart rate.
| Up to 21 days in Period 1, 2, 3 (Each period is 21 days); up to 25 days in Period 4 (Period 4 is 25 days) |
| Columbia-suicide Severity Rating Scale (C-SSRS) Score | The C-SSRS is a questionnaire scale to detect emergent suicide symptoms (suicidal ideation or actual suicidal behavior) during the course of this study. Questions are either answered yes/no or are on a scale of 1 (low severity) to 5 (high severity). | Up to 21 days in Period 1, 2, 3 (Each period is 21 days); up to 25 days in Period 4 (Period 4 is 25 days) |
| Number of Participants with Abnormalities in Clinical Laboratory Tests | Clinical laboratory assessments will include hematology, serum chemistry, coagulation, and urinalysis. | Up to 21 days in Period 1, 2, 3 (Each period is 21 days); up to 25 days in Period 4 (Period 4 is 25 days) |
| Number of Participants with Adverse Events (AEs) | An AE is any untoward medical occurrence associated with the use of a drug, whether or not considered drug-related. | Up to 28 Days After Last Dose of Study Drug (Up to 91 days)' |
| Number of Participants with Abnormalities in Physical Examinations | Physical examination will include, examination of skin, neurological, respiratory, cardiovascular, and gastrointestinal systems. | Up to 21 days in Period 1, 2, 3 (Each period is 21 days); up to 25 days in Period 4 (Period 4 is 25 days) |
| ID | Term |
|---|---|
| D009853 | Omeprazole |
| ID | Term |
|---|---|
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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