Trial Review

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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/NCT05758818




Registration number
NCT05758818
Ethics application status
Date submitted
29/01/2023
Date registered
7/03/2023
Date last updated
8/08/2023

Titles & IDs
Public title
A Study of Milademetan Administration on Cardiac Repolarization in Healthy Subjects
Scientific title
A Randomized, Positive and Placebo-Controlled Trial to Evaluate the Effects of Milademetan Administration on Cardiac Repolarization in Healthy Subjects
Secondary ID [1] 0 0
RAIN-3258
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiac Repolarization 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - Moxifloxacin (positive control)
Treatment: Drugs - Milademetan

Placebo Comparator: A = Placebo (negative control) - Dosage Form: Capsules
Route of Administration: Oral
The placebo and milademetan will be identical in appearance.

Active Comparator: B = Moxifloxacin (positive control) - Dosage Form: Tablets
Route of Administration: Oral
Dosage: 400 mg

Experimental: C = Milademetan - Drug: Milademetan
Dosage:
Part 1: 300, 330, 360 mg. Part 2: 260 mg single oral dose or higher, as determined in Part 1.


Treatment: Drugs: Placebo
Participants will receive a single dose of placebo on Day 1, Day 8 or Day 15 of part 2

Treatment: Drugs: Moxifloxacin (positive control)
Participants will receive a single dose of moxifloxacin on Day 1,Day 8, or Day 15 of Part 2

Treatment: Drugs: Milademetan
Participants will receive a single dose of Milademetan on Day 1 for part 1
Participants will receive a single dose of milademetan on Day 1, Day 8, or Day 15 of Part 2
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with adverse events (AEs)
Timepoint [1] 0 0
Part 1:Up to 15 days
Primary outcome [2] 0 0
Number of participants with adverse events (AEs)
Timepoint [2] 0 0
Part 2: Up to 25 days
Primary outcome [3] 0 0
Incidence of laboratory abnormalities based on hematology test results
Timepoint [3] 0 0
Part 1:Up to 15 days
Primary outcome [4] 0 0
Incidence of laboratory abnormalities based on hematology test results
Timepoint [4] 0 0
Part 2: Up to 25 days
Primary outcome [5] 0 0
Incidence of laboratory abnormalities based on clinical chemistry test results
Timepoint [5] 0 0
Part 1:Up to 15 days
Primary outcome [6] 0 0
Incidence of laboratory abnormalities based on clinical chemistry test results
Timepoint [6] 0 0
Part 2: Up to 25 days
Primary outcome [7] 0 0
Incidence of laboratory abnormalities based on urinalysis test results
Timepoint [7] 0 0
Part 1:Up to 15 days
Primary outcome [8] 0 0
Incidence of laboratory abnormalities based on urinalysis test results
Timepoint [8] 0 0
Part 2: Up to 25 days
Primary outcome [9] 0 0
Vital signs measurements
Timepoint [9] 0 0
Part 1:Up to 15 days
Primary outcome [10] 0 0
Vital signs measurements
Timepoint [10] 0 0
Part 2: Up to 25 days
Primary outcome [11] 0 0
Change from baseline in QT interval of the ECG
Timepoint [11] 0 0
Part 1:Up to 15 days
Primary outcome [12] 0 0
Change from baseline in QT interval of the ECG
Timepoint [12] 0 0
Part 2: Up to 25 days
Secondary outcome [1] 0 0
Observed maximum plasma concentration (Cmax)
Timepoint [1] 0 0
Part 1:Up to 15 days
Secondary outcome [2] 0 0
Observed maximum plasma concentration (Cmax)
Timepoint [2] 0 0
Part 2: Up to 25 days
Secondary outcome [3] 0 0
Time to observed maximum concentration (Tmax)
Timepoint [3] 0 0
Part 1:Up to 15 days
Secondary outcome [4] 0 0
Time to observed maximum concentration (Tmax)
Timepoint [4] 0 0
Part 2: Up to 25 days
Secondary outcome [5] 0 0
area under the time-concentration curve from time zero to the time of the last quantifiable concentration (AUC0-tlast)
Timepoint [5] 0 0
Part 1:Up to 15 days
Secondary outcome [6] 0 0
area under the time-concentration curve from time zero to the time of the last quantifiable concentration (AUC0-tlast)
Timepoint [6] 0 0
Part 2: Up to 25 days

Eligibility
Key inclusion criteria
1. Is capable of understanding informed consent and is willing and able to provide
written informed consent.

2. Is willing to comply with all protocol procedures.

3. Healthy, male, nonsmoking (for at least 90 days) subjects from 18 through 55 years of
age, inclusive, at Screening, and healthy, female, nonsmoking (for at least 90 days)
subjects of nonchildbearing potential from 18 through 55 years of age, inclusive, at
Screening.

4. Body weight > 50 kg, body mass index between 18.0 and 30 kg/m2, inclusive.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Past or present clinically relevant systemic disease as judged by the Investigator
including, but not limited to, clinically relevant medical abnormalities such as
psychiatric, neurologic, pulmonary, respiratory, cardiac, gastrointestinal,
genitourinary, renal, hepatic, metabolic, endocrinologic, hematological, or autoimmune
disorders making implementation of the protocol or interpretation of the study results
difficult, or that would put the subject at risk by participating in the study in the
opinion of the Investigator.

2. History of significant hypersensitivity, intolerance, or allergy to any drug compound,
food, or other substance, unless approved by the Investigator (or designee).

3. Knowledge of any kind of cardiovascular disorder/condition/procedure known to increase
the possibility of QT prolongation or a history of additional risk factors for torsade
de pointes (eg, heart failure, hypokalemia, hypomagnesemia, congenital long QT
syndrome, or family history of long QT syndrome, or Brugada syndrome), or cardiac
conduction disorders.

4. Resting supine systolic blood pressure greater than 140 mm Hg; resting supine
diastolic blood pressure greater than 90 mm Hg at Screening or Day -1. Blood pressure
measurements may be repeated once at the discretion of the Investigator.

5. Resting supine HR less than 45 beats per minute or greater than 100 beats per minute
at Screening or Day -1 (may be repeated once at the discretion of the Investigator).
Minor deviations are acceptable if considered to be of no clinical significance by the
Investigator.

6. Abnormal 12-lead ECG at Screening or Day -1 (a single repeat is allowed), including:

1. QTcF > 450 msec

2. QRS > 110 msec

3. PR > 200 msec

4. Second or third-degree atrioventricular block

7. Any rhythm other than sinus rhythm, which is interpreted by the Investigator to be
clinically significant at Screening or Day -1.

8. Dosing in another clinical trial within the last 30 days (or 5 half-lives, whichever
is longer) prior to Day -1.

9. Family history of unexplainable sudden death at < 50 years of age.

10. History of unexplained loss of consciousness, unexplained syncope, unexplained
irregular heartbeats or palpitations, clinically significant head injury, or near
drowning with hospital admission.

11. Known allergic reactions to moxifloxacin (for Part 2 only) or any study medication or
history of tendonitis or tendon rupture as a result of moxifloxacin or any other
quinolone type drug use (for Part 2 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
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/04/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/06/2023
Sample size
Target
Accrual to date
Final
6
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Nucleus Network Melbourne - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Rain Oncology Inc
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This will be a Phase 1, single-center, 2-part study in healthy subjects. Parts 1 and 2 need
to be conducted in sequential order.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05758818
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05758818