A Study of Milademetan Administration on Cardiac Repolarization in Healthy Subjects

NCT05758818 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: RAIN-3258
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiac Repolarization

Outcome Measures

Primary Outcomes (12)

• Number of participants with adverse events (AEs)

  The intensity of all AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  Part 1:Up to 15 days

• Number of participants with adverse events (AEs)

  The intensity of all AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  Part 2: Up to 25 days

• Incidence of laboratory abnormalities based on hematology test results

  Hematocrit, Hemoglobin, Mean cell hemoglobin

  Part 1:Up to 15 days

• Incidence of laboratory abnormalities based on hematology test results

  Hematocrit, Hemoglobin, Mean cell hemoglobin

  Part 2: Up to 25 days

• Incidence of laboratory abnormalities based on clinical chemistry test results

  Alanine aminotransferase, Albumin, Alkaline phosphatase, Aspartate aminotransferase

  Part 1:Up to 15 days

• Incidence of laboratory abnormalities based on clinical chemistry test results

  Alanine aminotransferase, Albumin, Alkaline phosphatase, Aspartate aminotransferase

  Part 2: Up to 25 days

• Incidence of laboratory abnormalities based on urinalysis test results

  Bilirubin, color and appearance, glucose, ketones, protein

  Part 1:Up to 15 days

• Incidence of laboratory abnormalities based on urinalysis test results

  Bilirubin, color and appearance, glucose, ketones, protein

  Part 2: Up to 25 days

• Vital signs measurements

  Supine systolic blood pressure in mmHg and supine diastolic blood pressure in mmHg

  Part 1:Up to 15 days

• Vital signs measurements

  Supine systolic blood pressure in mmHg and supine diastolic blood pressure in mmHg

  Part 2: Up to 25 days

• Change from baseline in QT interval of the ECG

  QT interval measured in msec

  Part 1:Up to 15 days

• Change from baseline in QT interval of the ECG

  QT interval measured in msec

  Part 2: Up to 25 days

Secondary Outcomes (6)

• Observed maximum plasma concentration (Cmax)

  Part 1:Up to 15 days

• Observed maximum plasma concentration (Cmax)

  Part 2: Up to 25 days

• Time to observed maximum concentration (Tmax)

  Part 1:Up to 15 days

• Time to observed maximum concentration (Tmax)

  Part 2: Up to 25 days

• area under the time-concentration curve from time zero to the time of the last quantifiable concentration (AUC0-tlast)

  Part 1:Up to 15 days

Study Arms (3)

A = Placebo (negative control)

PLACEBO COMPARATOR

Dosage Form: Capsules Route of Administration: Oral The placebo and milademetan will be identical in appearance.

Drug: Placebo

B = Moxifloxacin (positive control)

ACTIVE COMPARATOR

Dosage Form: Tablets Route of Administration: Oral Dosage: 400 mg

Drug: Moxifloxacin (positive control)

C = Milademetan

EXPERIMENTAL

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

Drug: Milademetan

Interventions

Placebo DRUG

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

A = Placebo (negative control)

Moxifloxacin (positive control) DRUG

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

B = Moxifloxacin (positive control)

Milademetan 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

C = Milademetan

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Is capable of understanding informed consent and is willing and able to provide written informed consent.
• Is willing to comply with all protocol procedures.
• 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.
• Body weight \> 50 kg, body mass index between 18.0 and 30 kg/m2, inclusive.

You may not qualify if:

• 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.
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
• 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.
• 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.
• 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.
• Abnormal 12-lead ECG at Screening or Day -1 (a single repeat is allowed), including:
• QTcF \> 450 msec
• QRS \> 110 msec
• PR \> 200 msec
• Second or third-degree atrioventricular block
• Any rhythm other than sinus rhythm, which is interpreted by the Investigator to be clinically significant at Screening or Day -1.
• Dosing in another clinical trial within the last 30 days (or 5 half-lives, whichever is longer) prior to Day -1.
• Family history of unexplainable sudden death at \< 50 years of age.
• History of unexplained loss of consciousness, unexplained syncope, unexplained irregular heartbeats or palpitations, clinically significant head injury, or near drowning with hospital admission.
• 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).

Sponsors & Collaborators

• Rain Oncology Inc: lead

Study Sites (1)

Nucleus Network Melbourne

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Interventions

Moxifloxacin; milademetan

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2023
• First Posted: March 7, 2023
• Study Start: April 17, 2023
• Primary Completion: June 8, 2023
• Study Completion: June 8, 2023
• Last Updated: August 8, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)