A Study of Milademetan Administration on Cardiac Repolarization in Healthy Subjects

NCT ID: NCT05758818

Last Updated: 2023-08-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-17
• Study Completion Date: 2023-06-08

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.

Detailed Description

Part 1 will enroll up to 3 cohorts of 6 healthy adult subjects to receive a single dose. The total duration of participation from the Screening visit to the follow-up will be up to 7 weeks (up to 45 days).

Part 2 of this study will randomize approximately 32 subjects. The total duration of participation from the Screening visit to the follow-up will be up to 8 weeks (up to 55 days).

Conditions

Cardiac Repolarization

Study Design

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

Study Groups

A = Placebo (negative control)

Dosage Form: Capsules

Route of Administration: Oral

The placebo and milademetan will be identical in appearance.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

B = Moxifloxacin (positive control)

Dosage Form: Tablets

Route of Administration: Oral

Dosage: 400 mg

Group Type: ACTIVE_COMPARATOR

Moxifloxacin (positive control)

Intervention Type: DRUG

Participants will receive a single dose of moxifloxacin on Day 1,Day 8, or Day 15 of Part 2

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.

Group Type: EXPERIMENTAL

Milademetan

Intervention Type: DRUG

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

Interventions

Placebo

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

Intervention Type: DRUG

Moxifloxacin (positive control)

Participants will receive a single dose of moxifloxacin on Day 1,Day 8, or Day 15 of Part 2

Intervention Type: DRUG

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 Type: DRUG

Eligibility Criteria

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.

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Rain Oncology Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Nucleus Network Melbourne

Melbourne, Victoria, Australia

Countries

Australia

Other Identifiers

RAIN-3258

Identifier Type: -

Identifier Source: org_study_id