Cardiac RepolarizationPhase 1NCT05758818
A Study of Milademetan Administration on Cardiac Repolarization in Healthy Subjects
A Phase 1 study testing Milademetan in people with Cardiac Repolarization, run by Rain Oncology Inc at 1 site in Australia.
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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Cardiac Repolarization
- What is being tested?
- Milademetan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 1 siteAustralia
- Study dates
- 17 Apr 2023to 8 Jun 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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:
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- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Positive and Placebo-Controlled Trial to Evaluate the Effects of Milademetan Administration on Cardiac Repolarization in Healthy Subjects
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.
Read the 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
- Being tested
- Placebo, Moxifloxacin (positive control), Milademetan
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Participants will receive a single dose of placebo on Day 1, Day 8 or Day 15 of part 2
Moxifloxacin (positive control)Drug
Participants will receive a single dose of moxifloxacin on Day 1,Day 8, or Day 15 of Part 2
MilademetanDrug
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
| Study group | Role | What they receive |
|---|---|---|
| A = Placebo (negative control) | Placebo comparator | Dosage Form: Capsules
Route of Administration: Oral
The placebo and milademetan will be identical in appearance. Receives: Drug: Placebo |
| B = Moxifloxacin (positive control) | Active comparator | Dosage Form: Tablets
Route of Administration: Oral
Dosage: 400 mg Receives: 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. Receives: Drug: Milademetan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Part 2: Up to 25 days
Incidence of laboratory abnormalities based on hematology test results
Hematocrit, Hemoglobin, Mean cell hemoglobin
Measured: Part 1:Up to 15 days
Incidence of laboratory abnormalities based on hematology test results
Hematocrit, Hemoglobin, Mean cell hemoglobin
Measured: Part 2: Up to 25 days
Incidence of laboratory abnormalities based on clinical chemistry test results
Alanine aminotransferase, Albumin, Alkaline phosphatase, Aspartate aminotransferase
Measured: Part 1:Up to 15 days
Incidence of laboratory abnormalities based on clinical chemistry test results
Alanine aminotransferase, Albumin, Alkaline phosphatase, Aspartate aminotransferase
Measured: Part 2: Up to 25 days
Incidence of laboratory abnormalities based on urinalysis test results
Bilirubin, color and appearance, glucose, ketones, protein
Measured: Part 1:Up to 15 days
Incidence of laboratory abnormalities based on urinalysis test results
Bilirubin, color and appearance, glucose, ketones, protein
Measured: Part 2: Up to 25 days
Vital signs measurements
Supine systolic blood pressure in mmHg and supine diastolic blood pressure in mmHg
Measured: Part 1:Up to 15 days
Vital signs measurements
Supine systolic blood pressure in mmHg and supine diastolic blood pressure in mmHg
Measured: Part 2: Up to 25 days
Change from baseline in QT interval of the ECG
QT interval measured in msec
Measured: Part 1:Up to 15 days
Change from baseline in QT interval of the ECG
QT interval measured in msec
Measured: Part 2: Up to 25 days
Secondary outcomes (6)
Observed maximum plasma concentration (Cmax)
observed maximum plasma concentration in ng/ml
Measured: Part 1:Up to 15 days
Observed maximum plasma concentration (Cmax)
observed maximum plasma concentration in ng/ml
Measured: Part 2: Up to 25 days
Time to observed maximum concentration (Tmax)
time to observed maximum concentration in hour
Measured: Part 1:Up to 15 days
Time to observed maximum concentration (Tmax)
time to observed maximum concentration in hour
Measured: 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)
Expressed as ng/ml x hr
Measured: Part 1:Up to 15 days
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
Measured: Part 2: Up to 25 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2023
- Study start17 Apr 2023
- Primary completion8 Jun 2023
- Study completion8 Jun 2023
Why it stopped: sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiac RepolarizationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rain Oncology Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05758818
- Sponsor's protocol ID
- RAIN-3258
- Status last verified
- Aug 2023
- First submitted
- 29 Jan 2023
- Last updated
- 8 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Positive and Placebo-Controlled Trial to Evaluate the Effects of Milademetan Administration on Cardiac Repolarization in Healthy Subjects
- ClinicalTrials.gov ID
- NCT05758818
- Acronym / sponsor ID
- RAIN-3258
- Conditions
- Cardiac Repolarization
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: sponsor decision
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Rain Oncology IncIndustry (pharma, biotech, devices)
- Study start
- 17 Apr 2023 (actual)
- Primary completion
- 8 Jun 2023 (actual)
- Study completion
- 8 Jun 2023 (actual)
- First posted
- 7 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| A = Placebo (negative control) | Placebo comparator | Drug: PlaceboDosage Form: Capsules Route of Administration: Oral The placebo and milademetan will be identical in appearance. |
| B = Moxifloxacin (positive control) | Active comparator | Drug: Moxifloxacin (positive control)Dosage Form: Tablets Route of Administration: Oral Dosage: 400 mg |
| C = Milademetan | Experimental | Drug: MilademetanDrug: Milademetan Dosage: Part 1: 300, 330, 360 mg. Part 2: 260 mg single oral dose or higher, as determined in Part 1. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboParticipants will receive a single dose of placebo on Day 1, Day 8 or Day 15 of part 2 | Drug | A = Placebo (negative control) |
| Moxifloxacin (positive control)Participants will receive a single dose of moxifloxacin on Day 1,Day 8, or Day 15 of Part 2 | Drug | B = Moxifloxacin (positive control) |
| MilademetanParticipants 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 | Drug | C = Milademetan |
Primary outcome
Number of participants with adverse events (AEs)
Time frame: Part 1:Up to 15 days
The intensity of all AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Number of participants with adverse events (AEs)
Time frame: Part 2: Up to 25 days
The intensity of all AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Incidence of laboratory abnormalities based on hematology test results
Time frame: Part 1:Up to 15 days
Hematocrit, Hemoglobin, Mean cell hemoglobin
Incidence of laboratory abnormalities based on hematology test results
Time frame: Part 2: Up to 25 days
Hematocrit, Hemoglobin, Mean cell hemoglobin
Incidence of laboratory abnormalities based on clinical chemistry test results
Time frame: Part 1:Up to 15 days
Alanine aminotransferase, Albumin, Alkaline phosphatase, Aspartate aminotransferase
Incidence of laboratory abnormalities based on clinical chemistry test results
Time frame: Part 2: Up to 25 days
Alanine aminotransferase, Albumin, Alkaline phosphatase, Aspartate aminotransferase
Incidence of laboratory abnormalities based on urinalysis test results
Time frame: Part 1:Up to 15 days
Bilirubin, color and appearance, glucose, ketones, protein
Incidence of laboratory abnormalities based on urinalysis test results
Time frame: Part 2: Up to 25 days
Bilirubin, color and appearance, glucose, ketones, protein
Vital signs measurements
Time frame: Part 1:Up to 15 days
Supine systolic blood pressure in mmHg and supine diastolic blood pressure in mmHg
Vital signs measurements
Time frame: Part 2: Up to 25 days
Supine systolic blood pressure in mmHg and supine diastolic blood pressure in mmHg
Change from baseline in QT interval of the ECG
Time frame: Part 1:Up to 15 days
QT interval measured in msec
Change from baseline in QT interval of the ECG
Time frame: Part 2: Up to 25 days
QT interval measured in msec
6 secondary outcomes
Observed maximum plasma concentration (Cmax)
Time frame: Part 1:Up to 15 days
Observed maximum plasma concentration (Cmax)
Time frame: Part 2: Up to 25 days
Time to observed maximum concentration (Tmax)
Time frame: Part 1:Up to 15 days
Time to observed maximum concentration (Tmax)
Time frame: 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)
Time frame: Part 1:Up to 15 days
area under the time-concentration curve from time zero to the time of the last quantifiable concentration (AUC0-tlast)
Time frame: Part 2: Up to 25 days
Results and safety
The study was stopped early (reason given: sponsor decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Milademetan in people with Cardiac Repolarization, run by Rain Oncology Inc at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: sponsor decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with adverse events (AEs) (time frame: Part 1:Up to 15 days). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2023.