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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06205381




Registration number
NCT06205381
Ethics application status
Date submitted
19/12/2023
Date registered
16/01/2024
Date last updated
12/03/2024

Titles & IDs
Public title
Assessment of the Safety, Tolerability and Pharmacokinetics of AV078 in Healthy Volunteers
Scientific title
A Phase 1, Single And Multiple Ascending Dose, Food Effect, and Drug-Drug Interaction Study With Itraconazole, Midazolam and Fexofenadine Of Orally Administered AV078 In Healthy Adults
Secondary ID [1] 0 0
CL-078-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy Participants 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AV078
Treatment: Drugs - Placebo
Treatment: Drugs - Itraconazole
Treatment: Drugs - Midazolam
Treatment: Drugs - Fexofenadine

Experimental: 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.

Placebo Comparator: 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.

Other: 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.

Other: 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.


Treatment: Drugs: AV078
Oral solution containing active ingredient, AV078

Treatment: Drugs: Placebo
Oral solution with no active ingredients

Treatment: Drugs: Itraconazole
Once daily oral dose of 200 mg itraconazole administered for 9 days

Treatment: Drugs: Midazolam
2.5 mg midazolam administered orally on day 1 and day 18

Treatment: Drugs: Fexofenadine
120 mg fexofenadine administered orally on day 1 and day 18
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence and severity of treatment emergent adverse events (TEAEs).
Timepoint [1] 0 0
From screening (Day -42) to final visit post-treatment (Day 14 for Part A and Day 42 for Part B).
Primary outcome [2] 0 0
Occurrence of clinically significant changes in physical examination (including neurological assessment).
Timepoint [2] 0 0
From screening (Day -42) to final visit post-treatment (Day 14 for Part A and Day 42 for Part B).
Primary outcome [3] 0 0
Change in blood haematology values.
Timepoint [3] 0 0
From screening (Day -42) to final visit post-treatment (Day 14 for Part A and Day 42 for Part B).
Primary outcome [4] 0 0
Change in blood biochemisty values.
Timepoint [4] 0 0
From screening (Day -42) to final visit post-treatment (Day 14 for Part A and Day 42 for Part B).
Primary outcome [5] 0 0
Change in urinalysis values.
Timepoint [5] 0 0
From screening (Day -42) to final visit post-treatment (Day 14 for Part A and Day 42 for Part B).
Primary outcome [6] 0 0
Change in lipid panel values.
Timepoint [6] 0 0
From screening (Day -42) to final visit post-treatment (Day 14 for Part A and Day 42 for Part B).
Primary outcome [7] 0 0
Change in blood coagulation values.
Timepoint [7] 0 0
From screening (Day -42) to final visit post-treatment (Day 14 for Part A and Day 42 for Part B).
Primary outcome [8] 0 0
Clinically significant ECG findings.
Timepoint [8] 0 0
From screening (Day -42) to final visit post-treatment (Day 14 for Part A and Day 42 for Part B).
Primary outcome [9] 0 0
Monitor for the emergence of suicidal ideation and behaviour using the Columbia-Suicide Severity Rating Scale (C-SSRS).
Timepoint [9] 0 0
From screening (Day -42) to final visit post-treatment (Day 14 for Part A and Day 42 for Part B).
Primary outcome [10] 0 0
Pharmacokinetics measured by area under the concentration-time curve in fasted and fed state.
Timepoint [10] 0 0
Day 1 to Day 7 post-dose and final follow-up visit (Day 14)
Primary outcome [11] 0 0
Pharmacokinetics measured by the maximum plasma concentration (Cmax) in fasted and fed state.
Timepoint [11] 0 0
Day 1 to Day 7 post-dose and final follow-up visit (Day 14)
Primary outcome [12] 0 0
Effects of itraconazole on the pharmacokinetics of AV078 measured by area under the concentration-time curve.
Timepoint [12] 0 0
Day 1 to Day 15 post-dose and final follow-up visit (Day 23)
Primary outcome [13] 0 0
Effects of itraconazole on the pharmacokinetics of AV078 measured by the maximum plasma concentration (Cmax).
Timepoint [13] 0 0
Day 1 to Day 15 post-dose and final follow-up visit (Day 23)
Primary outcome [14] 0 0
Effects of AV078 on the pharmacokinetics of midazolam and fexofenadine measured by area under the concentration-time curve.
Timepoint [14] 0 0
Day 1, 2, 18 and 19 post-dose (midazolam) or Day 1-3, 18 and 19 post-dose (fexofenadine)
Primary outcome [15] 0 0
Effects of AV078 on the pharmacokinetics of midazolam and fexofenadine measured by the maximum plasma concentration (Cmax).
Timepoint [15] 0 0
Day 1, 2, 18 and 19 post-dose (midazolam) or Day 1-3, 18 and 19 post-dose (fexofenadine)
Secondary outcome [1] 0 0
Pharmacokinetics of AV078 measured by the area under the concentration-time curve.
Timepoint [1] 0 0
Day 1 to final visit post-treatment (Day 14 for Part A and Day 42 for Part B).
Secondary outcome [2] 0 0
Pharmacokinetics of AV078 measured by the maximum plasma concentration (Cmax).
Timepoint [2] 0 0
Day 1 to final visit post-treatment (Day 14 for Part A and Day 42 for Part B).
Secondary outcome [3] 0 0
Pharmacokinetics of AV078 measured by time of maximum plasma/whole blood concentration.
Timepoint [3] 0 0
Day 1 to final visit post-treatment (Day 14 for Part A and Day 42 for Part B).
Secondary outcome [4] 0 0
Pharmacokinetics of AV078 measured by terminal elimination half-life.
Timepoint [4] 0 0
Day 1 to final visit post-treatment (Day 14 for Part A and Day 42 for Part B).
Secondary outcome [5] 0 0
Pharmacokinetics of AV078 measured by fraction of drug excreted in urine.
Timepoint [5] 0 0
Day 1 to final visit post-treatment (Day 14 for Part A and Day 42 for Part B).
Secondary outcome [6] 0 0
Pharmacokinetics of AV078 measured by renal clearance from plasma/whole blood.
Timepoint [6] 0 0
Day 1 to final visit post-treatment (Day 14 for Part A and Day 42 for Part B).
Secondary outcome [7] 0 0
Change from baseline and placebo-corrected change from baseline in ECG parameter, QTcF including exposure response.
Timepoint [7] 0 0
Part A: Screening (Day -42) to Day 5 post-dose, and final follow-up visit (Day 14). Part B: Screening (Day -42) to Day 2 post-dose, then Day 4, 7, 10, 14, 15 and 18 post-dose, and final follow-up visit (Day 42)]
Secondary outcome [8] 0 0
Change from baseline and placebo-corrected change from baseline in ECG parameter - heart rate (HR)
Timepoint [8] 0 0
Part A: Screening (Day -42) to Day 5 post-dose, and final follow-up visit (Day 14). Part B: Screening (Day -42) to Day 2 post-dose, then Day 4, 7, 10, 14, 15 and 18 post-dose, and final follow-up visit (Day 42)]
Secondary outcome [9] 0 0
Change from baseline and placebo-corrected change from baseline in ECG parameter - PR interval
Timepoint [9] 0 0
Part A: Screening (Day -42) to Day 5 post-dose, and final follow-up visit (Day 14). Part B: Screening (Day -42) to Day 2 post-dose, then Day 4, 7, 10, 14, 15 and 18 post-dose, and final follow-up visit (Day 42)]
Secondary outcome [10] 0 0
Change from baseline and placebo-corrected change from baseline in ECG parameter - QRS interval
Timepoint [10] 0 0
Part A: Screening (Day -42) to Day 5 post-dose, and final follow-up visit (Day 14). Part B: Screening (Day -42) to Day 2 post-dose, then Day 4, 7, 10, 14, 15 and 18 post-dose, and final follow-up visit (Day 42)]
Secondary outcome [11] 0 0
Incidence and severity of treatment emergent adverse events (TEAEs)
Timepoint [11] 0 0
From screening (Day -42) to final visit post-treatment (Day 14 for Part C, Day 23 for Part D and Day 26 for Part E)
Secondary outcome [12] 0 0
Occurrence of clinically significant changes in physical examination (including neurological assessment).
Timepoint [12] 0 0
From screening (Day -42) to final visit post-treatment (Day 14 for Part C, Day 23 for Part D and Day 26 for Part E)
Secondary outcome [13] 0 0
Change in blood haematology values
Timepoint [13] 0 0
From screening (Day -42) to final visit post-treatment (Day 14 for Part C, Day 23 for Part D and Day 26 for Part E)
Secondary outcome [14] 0 0
Change in blood biochemistry values
Timepoint [14] 0 0
From screening (Day -42) to final visit post-treatment (Day 14 for Part C, Day 23 for Part D and Day 26 for Part E)
Secondary outcome [15] 0 0
Change in urinalysis values
Timepoint [15] 0 0
From screening (Day -42) to final visit post-treatment (Day 14 for Part C, Day 23 for Part D and Day 26 for Part E)
Secondary outcome [16] 0 0
Change in lipid panel values
Timepoint [16] 0 0
From screening (Day -42) to final visit post-treatment (Day 14 for Part C, Day 23 for Part D and Day 26 for Part E)
Secondary outcome [17] 0 0
Change in blood coagulation values
Timepoint [17] 0 0
From screening (Day -42) to final visit post-treatment (Day 14 for Part C, Day 23 for Part D and Day 26 for Part E)
Secondary outcome [18] 0 0
Monitor for the emergence of suicidal ideation and behaviour using the Columbia-Suicide Severity Rating Scale (C-SSRS)
Timepoint [18] 0 0
From screening (Day -42) to final visit post-treatment (Day 14 for Part C, Day 23 for Part D and Day 26 for Part E)

Eligibility
Key inclusion criteria
Key

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).

Key
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/01/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2024
Actual
Sample size
Target
136
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Nucleus Network Pty Ltd - Melbourne
Recruitment postcode(s) [1] 0 0
3220 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Aeovian Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT06205381
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Davis Ryman
Address 0 0
Chief Medical Officer, Aeovian Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Brittany Croft, PhD
Address 0 0
Country 0 0
Phone 0 0
+61 3 9089 8202
Fax 0 0
Email 0 0
b.croft@nucleusnetwork.com.au
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06205381