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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1166-8630 | Registry Identifier | WHO |
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The purpose of this study is to determine the effect of multiple oral doses of naltrexone/bupropion on the pharmacokinetics (PK) of a single oral dose of metformin.
The drug being tested in this study is naltrexone HCl and bupropion HCl Extended- Release fixed dose combination (NB) . This study will evaluate the potential effect of multiple oral doses of extended-release combination of naltrexone/bupropion on the PK of a single oral dose of metformin in healthy participants with normal renal function (defined as creatinine clearance [CrCl] greater than equal to [>=] 90 milliliter per minute [mL/min]/1.73 meter square [m^2]).
The study will enroll approximately 30 participants. Participants will receive:
Metformin 850 mg as a single dose alone and in combination with multiple doses of Naltrexone/Bupropion Naltrexone 8 mg/Bupropion 90 mg + Naltrexone 16 mg/Bupropion 180 mg as multiple doses alone and in combination with a single dose of metformin
All participants will be asked to take 1 tablet of metformin in the morning on Day 1 and Day 14, 1 tablet of naltrexone/bupropion twice daily from Day 3 through Day 5, and 2 tablets of naltrexone/bupropion twice daily from Day 6 through Day 15.
This single center trial will be conducted in the United States. The overall time to participate in this study is 73 days. Participants will be admitted on Day -1 (check in) and remain confined to the clinic until Day 16 and will be contacted by telephone 30 (±2) days after last dose of study drug for a follow-up assessment. Serial blood samples will be collected for PK assessments. Safety will be monitored throughout the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metformin + Naltrexone/Bupropion | Experimental | Metformin (850 mg, immediate release tablet, orally, once on Day 1 and Day 14) naltrexone/bupropion (8/90 mg/mg, extended-release tablets, orally, twice daily from Day 3 through Day 5 and 16/180 mg/mg, twice daily from Day 6 through Day 15. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Naltrexone/Bupropion | Drug | Naltrexone/Bupropion extended-release tablets. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cmax: Maximum Observed Plasma Concentration for Metformin Following a Single Dose of Metformin Administered Alone | Day 1: predose and at multiple timepoints (up to 48 hours) post-dose | |
| Cmax: Maximum Observed Plasma Concentration of Metformin Following a Single Dose of Metformin and multiple Doses of naltrexone/bupropion | Day 14: predose and at multiple timepoints (up to 48 hours) post-dose | |
| AUC(0-inf): Area Under the Plasma Concentration-time Curve from Time 0 to Infinity of Metformin Following a Single Dose of Metformin Administered Alone | Day 1: predose and at multiple timepoints (up to 48 hours) post-dose | |
| AUC(0-inf): Area Under the Plasma Concentration-time Curve from Time 0 to Infinity of Metformin Following a Single Dose of Metformin and Multiple Doses of naltrexone/bupropion | Day 14: predose and at multiple timepoints (up to 48 hours) post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax: Maximum Observed Plasma Concentration of bupropion, naltrexone and their metabolites (6beta-naltrexol, Bupropion, Hydroxybupropion, Threohydrobupropion, and Erythrohydrobupropion) following multiple doses of NB alone | Day 13 predose and at multiple timepoints (up to 12 hours) post-dose | |
| Cmax: Maximum Observed Plasma Concentration of bupropion, naltrexone and their metabolites following multiple doses of naltrexone/bupropion and a single dose of metformin |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Takeda | Study Director |
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| ID | Term |
|---|---|
| D009271 | Naltrexone |
| D016642 | Bupropion |
| D008687 | Metformin |
| ID | Term |
|---|---|
| D009270 | Naloxone |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006571 |
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| Metformin | Drug | Metformin immediate-release tablet. |
|
| Day 14: predose and at multiple timepoints (up to 12 hours) post-dose |
| AUC(0-tau): Area Under the Plasma Concentration-time Curve during a dosing interval for upropion, naltrexone and their metabolites (6beta-naltrexol, Bupropion, Hydroxybupropion, Threohydrobupropion, and Erythrohydrobupropion) | Day 13: predose and at multiple timepoints (up to 12 hours) post-dose for naltrexone/buprop alone, Day 14: predose and at multiple timepoints (up to 12 hours) post-dose, Day 14: predose and at multiple timepoints (up to 48 hours) post-dose |
| • Percentage of Participants who Experience at Least one Treatment Emergent Adverse Event (TEAE) | Day 1 upt to Day 45 |
| Heterocyclic Compounds |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D011427 | Propiophenones |
| D007659 | Ketones |
| D009930 | Organic Chemicals |
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |