Assessment of the Safety, Tolerability and Pharmacokinetics of AV078 in Healthy Volunteers

NCT ID: NCT06205381

Last Updated: 2025-03-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 89 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-31
• Study Completion Date: 2025-02-08

Brief Summary

This Phase 1 study in healthy adult volunteers is planned to evaluate the safety, tolerability, and pharmacokinetics (PK) of AV078, a selective inhibitor of mammalian target of rapamycin complex 1 (mTORC1).

The study will begin with a standard exploration of safety and tolerability in sequential single ascending dose (SAD) and multiple ascending dose (MAD) cohorts. Subsequent cohorts will collect PK data to evaluate food effects and potential drug-drug interactions relevant to AV078.

Detailed Description

This Phase 1 study in healthy adult volunteers is planned to evaluate the safety, tolerability, and pharmacokinetics (PK) of AV078, a selective inhibitor of mammalian target of rapamycin complex 1 (mTORC1). The study will additionally explore the relationship between AV078 and pharmacodynamic biomarkers related to mTOR.

The study will begin with a standard exploration of safety and tolerability in sequential single ascending dose (SAD) and multiple ascending dose (MAD) cohorts, incorporating reviews by a dedicated Safety Review Group to guide dose escalation decisions. The study will also include a cohort using a 2-way crossover design to evaluate food effects on the PK of AV078. The study will additionally include cohorts evaluating potential drug-drug-interactions (DDIs) using coadministration of index substrates and index perpetrators typically used in DDI studies of the relevant enzymes. Specifically, one DDI cohort will assess the effects of administration of itraconazole (a strong inhibitor of CYP3A4) on the PK of AV078, and an additional DDI cohort will assess the effects of administration of AV078 on the PK of midazolam (a sensitive probe substrate for CYP3A4) and fexofenadine (a probe substrate for P-gp).

Conditions

Healthy Participants

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

AV078

In part A, a single ascending doses of AV078 oral solution will be investigated in separate cohorts. The starting dose will be 0.5 mg and ascending doses will be determined based on data from previous cohorts.

In Part B, multiple ascending doses of AV078 oral solution will be administered once daily for 14 days. Dose levels will be determined based on data from the single ascending dose study and previous cohorts in the multiple ascending dose study.

In Part C the effect of food (fasting or high calorie) on the pharmacokinetics of a single dose of AV078 will be investigated. The dose will be determined from Part A of the study.

Group Type: EXPERIMENTAL

AV078

Intervention Type: DRUG

Oral solution containing active ingredient, AV078

Placebo

In Part A, placebo oral solution (containing no active ingredient) will be administered once.

In Part B, placebo oral solution (containing no active ingredient) will be administered once daily for 14 days.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral solution with no active ingredients

Itraconazole

In Part D, 200 mg itraconazole will be administered as an oral capsule once daily for 9 days, to investigate the effect of itraconazole on the pharmacokinetics of AV078.

Group Type: OTHER

Itraconazole

Intervention Type: DRUG

Once daily oral dose of 200 mg itraconazole administered for 9 days

Midazolam and fexofenadine

In Part E, 2.5 mg midazolam will be administered as an oromucosal solution and 120 mg fexofenadine will be administered as an oral tablet on day 1 and day 18, to investigate the effect of AV078 on the pharmacokinetics of midazolam and fexofenadine.

Group Type: OTHER

Midazolam

Intervention Type: DRUG

2.5 mg midazolam administered orally on day 1 and day 18

Fexofenadine

Intervention Type: DRUG

120 mg fexofenadine administered orally on day 1 and day 18

Interventions

AV078

Oral solution containing active ingredient, AV078

Intervention Type: DRUG

Placebo

Oral solution with no active ingredients

Intervention Type: DRUG

Itraconazole

Once daily oral dose of 200 mg itraconazole administered for 9 days

Intervention Type: DRUG

Midazolam

2.5 mg midazolam administered orally on day 1 and day 18

Intervention Type: DRUG

Fexofenadine

120 mg fexofenadine administered orally on day 1 and day 18

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Healthy male or female as determined by medical evaluation including medical history, psychiatric history, and no clinically significant findings on physical examination, laboratory tests, and cardiac monitoring. Slight excursions outside of normal limits may be allowed provided they are considered not clinically significant by the investigator.

2. Ages 18-65 years (inclusive), at the time of consent.

3. At least 45 kg with a body mass index (BMI; Quetelet index) in the range 18.0-32.0, at screening.

4. Sufficient intelligence to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial.

5. Willingness to give written consent to participate after reading the information and consent form, and after having the opportunity to discuss the trial with the investigator or their delegate.

6. Agree not to donate blood or blood products during the study and for up to 3 months after the last administration of the trial medication.

7. Have received at least 2 doses of the COVID vaccine (1 dose of the Janssen-Cilag vaccine is acceptable).

Exclusion Criteria

1. Current, or past history of any clinically significant mental or physical illness or condition that the Investigator concludes would create significant concern for participation in the study.

2. Surgery (eg stomach bypass) or medical condition that might affect absorption of medicines (cholecystectomy is allowed).

3. Presence or history of severe adverse reaction to any drug or a history of sensitivity to midazolam (Part E only), fexofenadine (Part E only) and itraconazole (Part D only), or any excipients in the tablets/solutions.

4. History of relevant atopy including any confirmed significant allergic reactions against any drug, or multiple drug allergies (non-active hay fever is acceptable)

5. History of suicidal behaviour or express or have any suicidal ideation on the C-SSRS at screening or admission.

6. Employee of the Sponsor, the CRO and/or study site or their relatives.

7. Unable or unwilling to eat a high-fat breakfast per study requirements (Part C only).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Aeovian Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Davis Ryman

Role: STUDY_DIRECTOR

Chief Medical Officer, Aeovian Pharmaceuticals

Locations

Q-Pharm

Herston, Queensland, Australia

Nucleus Network Pty Ltd

Melbourne, Victoria, Australia

Countries

Australia

Other Identifiers

CL-078-101

Identifier Type: -

Identifier Source: org_study_id