Clinical trial NCT05758818: A Study of Milademetan Administration on Cardiac Repolarization in Healthy Subjects
Official title: A Randomized, Positive and Placebo-Controlled Trial to Evaluate the Effects of Milademetan Administration on Cardiac Repolarization in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Cardiac Repolarization
Lead sponsor: Rain Oncology Inc
Sponsor class: INDUSTRY
First posted: 2023-03-07
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

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).

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: Part 1:Up to 15 days
measure: Number of participants with adverse events (AEs)
timeFrame: Part 2: Up to 25 days
measure: Incidence of laboratory abnormalities based on hematology test results
timeFrame: Part 1:Up to 15 days
measure: Incidence of laboratory abnormalities based on hematology test results
timeFrame: Part 2: Up to 25 days
measure: Incidence of laboratory abnormalities based on clinical chemistry test results
timeFrame: Part 1:Up to 15 days
measure: Incidence of laboratory abnormalities based on clinical chemistry test results
timeFrame: Part 2: Up to 25 days
measure: Incidence of laboratory abnormalities based on urinalysis test results
timeFrame: Part 1:Up to 15 days
measure: Incidence of laboratory abnormalities based on urinalysis test results
timeFrame: Part 2: Up to 25 days
measure: Vital signs measurements
timeFrame: Part 1:Up to 15 days
measure: Vital signs measurements
timeFrame: Part 2: Up to 25 days
measure: Change from baseline in QT interval of the ECG
timeFrame: Part 1:Up to 15 days
measure: Change from baseline in QT interval of the ECG
timeFrame: Part 2: Up to 25 days
Secondary outcomes:
measure: Observed maximum plasma concentration (Cmax)
timeFrame: Part 1:Up to 15 days
measure: Observed maximum plasma concentration (Cmax)
timeFrame: Part 2: Up to 25 days
measure: Time to observed maximum concentration (Tmax)
timeFrame: Part 1:Up to 15 days
measure: Time to observed maximum concentration (Tmax)
timeFrame: Part 2: Up to 25 days
measure: area under the time-concentration curve from time zero to the time of the last quantifiable concentration (AUC0-tlast)
timeFrame: Part 1:Up to 15 days
measure: area under the time-concentration curve from time zero to the time of the last quantifiable concentration (AUC0-tlast)
timeFrame: Part 2: Up to 25 days
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Nucleus Network Melbourne
state: Victoria
Study officials:
References: