NCT06406400

Drug-Drug Interaction and Safety of AZD4041 Study (Part 1) and Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of AZD4041 Study in Opioid Use Disorder (Part 2).

A Two-Part Study to Examine the Drug-Drug Interaction With Itraconazole and Safety of AZD4041 in Healthy Participants and the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of AZD4041 as an Adjunctive Treatment to Buprenorphine in Participants With Moderate to Severe Opioid Use Disorder

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (actual)
• Sponsor: AstraZeneca · Industry
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The purpose of the study is to assess drug-drug interaction (DDI) and safety of AZD4041 and itraconazole in healthy participants (Part 1), and to assess efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of AZD404 when administered with buprenorphine/buprenorphine + naloxone in participants with moderate to severe opioid use disorder (OUD)

Detailed description

This study will be conducted in 2 sequential parts. Part 1 (Phase I) will include healthy participants and will be conducted as two separate parts. Part 1a (DDI cohort) is an open-label, fixed sequence study part which will comprise of: * A Screening Period from Day -28 to Day -3. * Three treatment periods: * Period 1 (Day -2 to Day 5): Participants will be admitted to the clinical unit on Day -2 and will receive a single oral dose of AZD4041 on Day 1. There will be a 5-day washout period. * Period 2 (Day 6 to Day 8): Participants will receive itraconazole for 3 days from Day 6 through Day 8. * Period 3 (Day 9 to Day 22): On Day 9, participants will receive single oral dose of AZD4041 co-administered with itraconazole. Itraconazole alone will be administered from Day 10 to Day 21. * A Follow-up Visit: Participants will return to the clinical unit at least 7 days and no later than 14 days after discharge. Based on the results from Part 1a, an optional part of the study (Part 1b) may be conducted to assess the safety tolerability and PK of AZD4041 after a single oral dose. Part 1b (Single Dose Cohort) will be a randomized, placebo-controlled, double-blind (participant and investigator blinded) study part conducted in healthy participants. This study part will comprise of the following: * A Screening Period from Day -28 to Day -3. * A Treatment Period: Participants will be admitted to the clinical unit on Day -2 and will remain in the unit until Day 4, when they will be discharged after completion of all assessments. * A Follow-up Visit: Participant will return to the clinical unit at least 12 days and no greater than 16 days after the last AZD4041 PK sample. The results from Part 1 will determine the AZD4041 dose selection and safety margin to be used in Part 2. Part 2 (Phase IIa) will be a randomized, placebo-controlled, double-blind study. Participants will be randomized to 1 of 2 treatment arms, AZD4041 or placebo, in a 1:1 ratio. Part 2 will consist of: * A Screening Period from Day -21 to Day -2. * A Treatment Period: Participants will be admitted to the clinical unit on Day -1 and will receive either AZD4041 or placebo with hydromorphone (as a replacement opioid) on Days 1, 2 and 3, and buprenorphine/buprenorphine + naloxone (as a standard of care for their opioid withdrawal) on Days 4, 5, 6 and 7. Participants who complete the treatment period will have continued access to Suboxone (buprenorphine + naloxone) during their Follow-up period, which will be supplied to participants at discharge (Day 7). * A Follow-up Visit: Participant will return to the clinical unit at least 7 days and no greater than 9 days after the last AZD4041 dose.

Conditions

• Opioid Use Disorder

Interventions

Type	Name	Description
DRUG	AZD4041	Part 1a: Healthy participants will receive AZD4041 (Dose 1) orally on Day 1 and Day 9. Part 1b: Healthy participants will receive AZD4041 (Dose 2) orally on Day 1 as a single dose. Part 2: Participants with OUD will receive daily doses of AZD4041 from Days 1 to 7.
DRUG	Itraconazole	Healthy participants will receive itraconazole orally from Days 6 to 8 in Period 2 and Days 9 to 21 in Period 3.
DRUG	Buprenorphine	Participants with OUD will receive buprenorphine (as standard of care treatment) on Day 4.
DRUG	Buprenorphine / Naloxone	Participants with OUD will receive buprenorphine + naloxone (as standard of care treatment) on Days 4, 5, 6 and 7
DRUG	Hydromorphone	Participants with OUD will receive hydromorphone (as a replacement opioid) on Days 1, 2 and 3.
DRUG	Placebo	Part 1b: Healthy participants will receive matching placebo orally on Day 1 as a single dose. Part 2: Participants with OUD will receive placebo daily from Days 1 to 7.

Timeline

• Start date: 2024-05-13
• Primary completion: 2024-07-31
• Completion: 2024-07-31
• First posted: 2024-05-09
• Last updated: 2025-03-26

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study