A Study of Milademetan Administration on Cardiac Repolarization in Healthy Subjects

Cardiac Repolarization Clinical Trial

Official title:

A Randomized, Positive and Placebo-Controlled Trial to Evaluate the Effects of Milademetan Administration on Cardiac Repolarization in Healthy Subjects

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05758818
• Other study ID #: RAIN-3258
• Status: Terminated
• Phase: Phase 1
• Start date: April 17, 2023
• Est. completion date: June 8, 2023

Study information

• Verified date: August 2023
• Source: Rain Oncology Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: June 8, 2023
• Est. primary completion date: June 8, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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).

Related Conditions & MeSH terms

• Cardiac Repolarization

Intervention

Drug:
• Placebo
Participants will receive a single dose of placebo on Day 1, Day 8 or Day 15 of part 2
• Moxifloxacin (positive control)
Participants will receive a single dose of moxifloxacin on Day 1,Day 8, or Day 15 of Part 2
• 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

Locations

Country	Name	City	State
Australia	Nucleus Network Melbourne	Melbourne	Victoria

Sponsors (1)

Lead Sponsor	Collaborator
Rain Oncology Inc

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Incidence of laboratory abnormalities based on hematology test results	Hematocrit, Hemoglobin, Mean cell hemoglobin	Part 1:Up to 15 days
Primary	Incidence of laboratory abnormalities based on hematology test results	Hematocrit, Hemoglobin, Mean cell hemoglobin	Part 2: Up to 25 days
Primary	Incidence of laboratory abnormalities based on clinical chemistry test results	Alanine aminotransferase, Albumin, Alkaline phosphatase, Aspartate aminotransferase	Part 1:Up to 15 days
Primary	Incidence of laboratory abnormalities based on clinical chemistry test results	Alanine aminotransferase, Albumin, Alkaline phosphatase, Aspartate aminotransferase	Part 2: Up to 25 days
Primary	Incidence of laboratory abnormalities based on urinalysis test results	Bilirubin, color and appearance, glucose, ketones, protein	Part 1:Up to 15 days
Primary	Incidence of laboratory abnormalities based on urinalysis test results	Bilirubin, color and appearance, glucose, ketones, protein	Part 2: Up to 25 days
Primary	Vital signs measurements	Supine systolic blood pressure in mmHg and supine diastolic blood pressure in mmHg	Part 1:Up to 15 days
Primary	Vital signs measurements	Supine systolic blood pressure in mmHg and supine diastolic blood pressure in mmHg	Part 2: Up to 25 days
Primary	Change from baseline in QT interval of the ECG	QT interval measured in msec	Part 1:Up to 15 days
Primary	Change from baseline in QT interval of the ECG	QT interval measured in msec	Part 2: Up to 25 days
Secondary	Observed maximum plasma concentration (Cmax)	observed maximum plasma concentration in ng/ml	Part 1:Up to 15 days
Secondary	Observed maximum plasma concentration (Cmax)	observed maximum plasma concentration in ng/ml	Part 2: Up to 25 days
Secondary	Time to observed maximum concentration (Tmax)	time to observed maximum concentration in hour	Part 1:Up to 15 days
Secondary	Time to observed maximum concentration (Tmax)	time to observed maximum concentration in hour	Part 2: Up to 25 days
Secondary	area under the time-concentration curve from time zero to the time of the last quantifiable concentration (AUC0-tlast)	Expressed as ng/ml x hr	Part 1:Up to 15 days
Secondary	area under the time-concentration curve from time zero to the time of the last quantifiable concentration (AUC0-tlast)	Expressed as ng/ml x hr	Part 2: Up to 25 days