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| Name | Class |
|---|---|
| Parexel | INDUSTRY |
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The purpose of this study is to measure the effect of multiple doses of AZD2389 on the pharmacokinetics (PK) of midazolam, caffeine, and bupropion in healthy participants.
This study is an open-label, fixed sequence, 3-period, drug-drug interaction (DDI) study in healthy participants performed at a single Clinical Unit.
The study will comprise:
Period 2 (Day 5 to Day 13): Participants will receive AZD2389 for 9 days. Period 3 (Day 14 to Day 18): Participants will first receive AZD2389 with midazolam and caffeine in combination on Day 14. On Day 15, participants will first receive AZD2389 with bupropion. On Days 16 and 17, participants will receive AZD2389.
- A final Follow-up Visit, 7 to 14 days after the last AZD2389 PK sample is taken in Period 3.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment Arm | Experimental | In Period 1, participants will receive midazolam and caffeine in combination on Day 1. Participants will receive bupropion on Day 2. In Period 2, participants will receive AZD2389 for 9 days from Day 5 to Day 13. In Period 3, participants will first receive AZD2389 with midazolam and caffeine in combination on Day 14. On Day 15, participants will first receive AZD2389 with bupropion. On Days 16 and 17, participants will receive AZD2389. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD2389 | Drug | Oral dose on Days 5 to 13, Day 16, and Day 17. On Day 14 co-administered with a combination of midazolam and caffeine. On Day 15 co-administered with bupropion. |
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| Measure | Description | Time Frame |
|---|---|---|
| Ratio of treatment to reference based on Cmax (RCmax) | To assess the PK parameter RCmax for midazolam, caffeine, and bupropion in combination with AZD2389 compared to midazolam, caffeine, and bupropion alone. | Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18. |
| Ratio of treatment to reference based on AUCinf (RAUCinf) | To assess the PK parameter RAUCinf for midazolam, caffeine, and bupropion in combination with AZD2389 compared to midazolam, caffeine, and bupropion alone. | Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18. |
| Ratio of treatment to reference based on AUClast (RAUClast) | To assess the PK parameter RAUClast for midazolam, caffeine, and bupropion in combination with AZD2389 compared to midazolam, caffeine, and bupropion alone. | Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18. |
| Ratio of area under concentration-curve from time 0 to 24 hours post-dose (AUC0-24) | To assess the PK parameter ratio of AUC0-24 for caffeine in combination with AZD2389 compared to caffeine alone. | Period 1: Days 1-3; Period 3: Days 15-18. |
| Measure | Description | Time Frame |
|---|---|---|
| Apparent total body clearance (CL/F) | To describe the plasma PK of midazolam, caffeine, bupropion, and their metabolites (1'-OH-midazolam, paraxanthine, and hydroxy-bupropion) when midazolam, caffeine, or bupropion is administered alone and in combination with AZD2389. To describe the plasma PK of AZD2389 after multiple dose administration. | Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Brooklyn | Maryland | 21225 | United States |
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
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| Midazolam | Drug | Single oral dose on:
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| Caffeine | Drug | Single oral dose on:
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| Bupropion | Drug | Single oral dose on:
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| Apparent volume of distribution based on the terminal phase (Vz/F) | To describe the plasma PK of midazolam, caffeine, bupropion, and their metabolites (1'-OH-midazolam, paraxanthine, and hydroxy-bupropion) when midazolam, caffeine, or bupropion is administered alone and in combination with AZD2389. To describe the plasma PK of AZD2389 after multiple dose administration. | Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18. |
| Terminal elimination half-life (t1/2λz) | To describe the plasma PK of midazolam, caffeine, bupropion, and their metabolites (1'-OH-midazolam, paraxanthine, and hydroxy-bupropion) when midazolam, caffeine, or bupropion is administered alone and in combination with AZD2389. To describe the plasma PK of AZD2389 after multiple dose administration. | Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18. |
| Terminal rate constant (λz) | To describe the plasma PK of midazolam, caffeine, bupropion, and their metabolites (1'-OH-midazolam, paraxanthine, and hydroxy-bupropion) when midazolam, caffeine, or bupropion is administered alone and in combination with AZD2389. To describe the plasma PK of AZD2389 after multiple dose administration. | Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18. |
| Time to reach maximum observed concentration (tmax) | To describe the plasma PK of midazolam, caffeine, bupropion, and their metabolites (1'-OH-midazolam, paraxanthine, and hydroxy-bupropion) when midazolam, caffeine, or bupropion is administered alone and in combination with AZD2389. To describe the plasma PK of AZD2389 after multiple dose administration. | Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18. |
| Maximum observed concentration (Cmax) | To describe the plasma PK of midazolam, caffeine, bupropion, and their metabolites (1'-OH-midazolam, paraxanthine, and hydroxy-bupropion) when midazolam, caffeine, or bupropion is administered alone and in combination with AZD2389. To describe the plasma PK of AZD2389 after multiple dose administration. | Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18. |
| Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) | To describe the plasma PK of midazolam, caffeine, bupropion, and their metabolites (1'-OH-midazolam, paraxanthine, and hydroxy-bupropion) when midazolam, caffeine, or bupropion is administered alone and in combination with AZD2389. To describe the plasma PK of AZD2389 after multiple dose administration. | Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18. |
| Area under concentration-time curve from time 0 to infinity (AUCinf) | To describe the plasma PK of midazolam, caffeine, bupropion, and their metabolites (1'-OH-midazolam, paraxanthine, and hydroxy-bupropion) when midazolam, caffeine, or bupropion is administered alone and in combination with AZD2389. To describe the plasma PK of AZD2389 after multiple dose administration. | Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18. |
| AUC0-24 | To describe the plasma PK of caffeine and its metabolites (paraxanthine) when caffeine is administered alone and in combination with AZD2389. | Period 1: Days 1-3; Period 3: Days 15-18. |
| RCmax | To assess the RCmax for the metabolites of midazolam, caffeine, and bupropion (1'-OH-midazolam, paraxanthine, OH-bupropion) when midazolam, caffeine, or bupropion is administered alone and in combination with AZD2389. | Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18. |
| RAUCinf | To assess the RAUCinf for the metabolites of midazolam, caffeine, and bupropion (1'-OH-midazolam, paraxanthine, OH-bupropion) when midazolam, caffeine, or bupropion is administered alone and in combination with AZD2389. | Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18. |
| RAUClast | To assess the RAUClast for the metabolites of midazolam, caffeine, and bupropion (1'-OH-midazolam, paraxanthine, OH-bupropion) when midazolam, caffeine, or bupropion is administered alone and in combination with AZD2389. | Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18. |
| Ratio of treatment to reference based on AUC0-24 (RAUC0-24) | To assess the RAUC0-24 for the metabolites of caffeine, (paraxanthine) when caffeine is administered alone and in combination with AZD2389. | Period 1: Days 1-3; Period 3: Days 15-18. |
| Metabolite to parent ratio of the AUCinf | To assess the metabolite to parent ratio of the AUCinf for midazolam, caffeine, and bupropion. | Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18. |
| Metabolite to parent ratio of the AUC0-24 | To assess the metabolite to parent ratio of the AUC0-24 for caffeine and its metabolite (paraxanthine) when caffeine is administered alone and in combination with AZD2389. | Period 1: Days 1-3; Period 3: Days 15-18. |
| Area under concentration-time curve in the dose interval (AUCtau) | To describe the plasma PK of AZD2389 after multiple dose administration. | Period 2: Days 5-13; Period 3: Day 14. |
| Observed lowest concentration before the next dose is administered (Ctrough) | To describe the plasma PK of AZD2389 after multiple dose administration. | Period 2: Days 5-13; Period 3: Day 14. |
| Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) | To assess the safety and tolerability of multiple oral doses of AZD2389 alone or in combination with midazolam, caffeine and bupropion in healthy participants. | Only SAE: -30 to -3 to Day -1. AE and SAE: From Day 1 to Follow-up/Early Termination Visit (Days 25-32) |
| ID | Term |
|---|---|
| D008103 | Liver Cirrhosis |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D005355 | Fibrosis |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D008874 | Midazolam |
| D002110 | Caffeine |
| D016642 | Bupropion |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D014970 | Xanthines |
| D000470 | Alkaloids |
| D011688 | Purinones |
| D011687 | Purines |
| D011427 | Propiophenones |
| D007659 | Ketones |
| D009930 | Organic Chemicals |
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