Healthy VolunteerPhase 1NCT04411030
A Study to Investigate the Effect of CYP3A4 Inhibition on the Single Dose Pharmacokinetics of ASTX660 and the Effect of a Single Dose of ASTX660 on the Pharmacokinetics of the CYP3A4 Substrate Midazolam
A Phase 1 study testing ASTX660, Midazolam and Itraconazole in people with Healthy Volunteer, run by Astex Pharmaceuticals, Inc. at 1 site in United States.
Trial summary
In Part 1, the primary objective is to investigate the effect of multiple doses of itraconazole, an inhibitor of CYP3A4, on the pharmacokinetic (PK) profile of a single dose of ASTX660. Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteer
- What is being tested?
- ASTX660, Midazolam and Itraconazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 20 May 2020to 29 Aug 2020
- 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 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participant understands the study procedures and agrees to participate by providing written informed consent.
- Participant is willing and able to comply with all study procedures and restrictions.
- Participant is male aged 18 to 45 years, inclusive at Screening.
- Participant has a body mass index (BMI) ≥ 18.5 kg/m2 and ≤ 30.0 kg/m2 at Screening.
- Participant is considered medically healthy as determined by the investigator, based on clinical evaluations including medical history, physical examination, clinical laboratory tests, 12-lead electrocardiogram (ECG) in triplicate, and vital sign measurements performed at Screening.
- Participants must be willing to use adequate contraception (double-barrier) from screening until 3 months after study completion. Male vasectomy is accepted as contraception if the vasectomy took place ≥ 6 months prior to first dose.
- Participants must refrain from sperm donation, from screening until 3 months after study completion.
Who cannot join
- Participant is mentally or legally incapacitated or has significant emotional problems at the time of Screening or is expected to have such problems during the conduct of the study.
- Participant has a clinically significant medical or psychiatric condition or disease (acute or chronic) that, as judged by the investigator, would make the participant ineligible for participation in the study (eg, compromises the study data, limits the participant's ability to complete and/or participate in the study).
- Participant has a current condition or history of significant endocrine, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, urological, immunological, or neurological disorders with clinical manifestations that, as judged by the investigator, would make the participant ineligible for participation in the study.
- Participant has a chronic disease requiring medication, dietary restriction, physical therapy, and/or other routine treatment that, as judged by the investigator, would make the participant ineligible for participation in the study.
- Participant has a history of gastrointestinal (GI) surgery including but not limited to gastric resection and/or intestinal resection that resulted in a clinically significant abnormality in GI function.
- Participant has a history or presence of cancer (with the exception of a history of basal cell carcinoma of the skin).
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- Participant has a history of drug and/or alcohol addiction or is a current regular user (including recreational use) of any illicit drugs, has a history of drug or alcohol abuse, or has ever undergone drug or alcohol rehabilitation.
- Participant has a history of significant multiple and/or severe allergies (eg, food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerance to food, prescription drugs or non-prescription (over-the-counter) drugs. Note: participants with seasonal allergies may participate.
- Participant has a known history of coronavirus disease 2019 (COVID-19) or has had contact with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive or COVID-19 patient within the 4 weeks prior to admission to the study center.
- Participant has a QTcF interval of > 450 msec at Screening.
- Participant has an estimated creatinine clearance < 90 mL/min based on the Cockcroft Gault equation at Screening.
- Participant regularly consumes excessive amounts of caffeine, defined as > 6 servings of coffee, tea, cola, or other caffeinated beverages, per day (1 serving is approximately equivalent to 120 mg of caffeine).
- Participant regularly consumes excessive amounts of alcohol, defined as > 3 glasses of alcoholic beverages per day and/or refuses to refrain from consuming such products throughout the study.
- Participant has used any medication (including prescription or non-prescription drugs, dietary or vitamin/mineral supplements or herbal remedies that are known to induce drug-metabolizing enzymes) within 14 days (or 5 half-lives, whichever is longer) prior to study drug administration on Day 1.
- Participant has used any medications known to be significant CYP inducers, including St. John's wort, within 28 days prior to the study drug administration on Day 1.
- Participant has consumed grapefruit, grapefruit juice, grapefruit juice-containing products, Seville oranges, orange juice, and/or apple juice within 7 days prior to study drug administration on Day 1 and/or refuses to refrain from consuming such products throughout the study.
- Participant has consumed vegetables from the mustard green family (eg, kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard) and/or charbroiled meats within 7 days prior to study drug administration on Day 1 and/or refuses to refrain from consuming such products throughout the study.
- Participant has used tobacco- or nicotine-containing products (eg, cigarette, pipe, cigar, chewing, nicotine patch, or nicotine gum) within 6 months prior to Day -1.
- Participant refuses to refrain from using tobacco- or nicotine-containing products throughout the study.
- Participant has a positive urine drug and/or alcohol screening test result at Screening or on Day -1.
- Participant has a positive test result for any serological test including human immunodeficiency virus (HIV) antigen/antibody, Hepatitis B surface antigen (HBsAg), and Hepatitis C virus (HCV) antibody at Screening.
- Participant has a positive test result for SARS-CoV-2 antigen, either asymptomatic or present with COVID-19 at study check-in.
- Participant appears to have poor venous access.
- Participant has donated blood or had significant blood loss within 56 days of study drug administration on Day 1.
- Participant has donated plasma within 7 days prior to study drug administration on Day 1.
- Participant has participated in any other investigational trial or has received any investigational drug within 28 days (or 5 half-lives of the previous investigational drug). The date will be derived from the last study procedure [blood collection or dosing] of previous trial prior to study drug administration on Day 1.
- Participant has any hypersensitivity to the study drugs or any of their excipients.
- Participant is ineligible for this study for any other reason, as judged by the investigator.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Two Cohort, Open-Label, Fixed Sequence Study to Investigate the Effect of CYP3A4 Inhibition on the Single Dose Pharmacokinetics of ASTX660 and the Effect of a Single Dose of ASTX660 on the Pharmacokinetics of the CYP3A4 Substrate Midazolam
In Part 1, the primary objective is to investigate the effect of multiple doses of itraconazole, an inhibitor of CYP3A4, on the pharmacokinetic (PK) profile of a single dose of ASTX660.
In Part 2, the primary objective is to investigate the effect of a single dose of ASTX660 on the pharmacokinetics of the CYP3A4 substrate midazolam and its metabolite, 1-hydroxy midazolam.
Safety and tolerability of a single dose of ASTX660 in the absence and presence of multiple doses of the CYP3A4 inhibitor itraconazole and in the presence of a single dose of the CYP3A4 substrate midazolam will also be evaluated.
- Conditions
- Healthy Volunteer
- Being tested
- ASTX660, Midazolam, Itraconazole
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ASTX660Drug
Form: capsule; Route of administration: oral
MidazolamDrug
Form: syrup; Route of administration: oral
ItraconazoleDrug
Form: capsule; Route of administration: oral
| Study group | Role | What they receive |
|---|---|---|
| Part 1 | Experimental | Oral administration of ASTX660 and itraconazole at specific time points. Receives: Drug: ASTX660; Drug: Itraconazole |
| Part 2 | Experimental | Oral administration of ASTX660 and midazolam at specific time points. Receives: Drug: ASTX660; Drug: Midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic parameter of ASTX660: Cmax
Maximum plasma concentration
Measured: From predose up to Day 14
Pharmacokinetic parameter of ASTX660: AUC0-t
Area under the plasma concentration versus time curve from time zero to the last measurable concentration
Measured: From predose up to Day 14
Pharmacokinetic parameter of ASTX660: AUC0-24
Area under the plasma concentration versus time curve from time zero to 24 hours
Measured: From predose up to Day 14
Pharmacokinetic parameter of ASTX660: AUC0-inf
Area under the plasma concentration versus time curve from time zero extrapolated to infinity
Measured: From predose up to Day 14
Pharmacokinetic parameter of midazolam and 1-hydroxyl midazolam: Cmax
Maximum plasma concentration
Measured: From predose up to Day 9
Pharmacokinetic parameter of midazolam and 1-hydroxyl midazolam: AUC0-t
Area under the plasma concentration versus time curve from time zero to the last measurable concentration
Measured: From predose up to Day 9
Pharmacokinetic parameter of midazolam and 1-hydroxyl midazolam: AUC0-24
Area under the plasma concentration versus time curve from time zero to 24 hours
Measured: From predose up to Day 9
Pharmacokinetic parameter of midazolam and 1-hydroxyl midazolam: AUC0-inf
Area under the plasma concentration versus time curve from time zero extrapolated to infinity
Measured: From predose up to Day 9
Secondary outcomes (5)
Pharmacokinetic parameter for ASTX660: CL/F
Total apparent clearance
Measured: From predose up to Day 14
Pharmacokinetic parameter for ASTX660: t1/2
Observed terminal half-life
Measured: From predose up to Day 14
Pharmacokinetic parameter for midazolam: CL/F
Total apparent clearance
Measured: From predose up to Day 9
Pharmacokinetic parameter for midazolam: t1/2
Observed terminal half-life
Measured: From predose up to Day 9
Safety: Number of participants with adverse events
Measured: Up to Day 35
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2020
- Study start20 May 2020
- Primary completion23 Aug 2020
- Study completion29 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteerStudies 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astex Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04411030
- Sponsor's protocol ID
- ASTX660-12
- Status last verified
- Aug 2024
- First submitted
- 29 May 2020
- Last updated
- 2 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- 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 2 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two Cohort, Open-Label, Fixed Sequence Study to Investigate the Effect of CYP3A4 Inhibition on the Single Dose Pharmacokinetics of ASTX660 and the Effect of a Single Dose of ASTX660 on the Pharmacokinetics of the CYP3A4 Substrate Midazolam
- ClinicalTrials.gov ID
- NCT04411030
- Acronym / sponsor ID
- ASTX660-12
- Conditions
- Healthy Volunteer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Astex Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 20 May 2020 (actual)
- Primary completion
- 23 Aug 2020 (actual)
- Study completion
- 29 Aug 2020 (actual)
- First posted
- 1 Jun 2020 (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.
In Part 1, the primary objective is to investigate the effect of multiple doses of itraconazole, an inhibitor of CYP3A4, on the pharmacokinetic (PK) profile of a single dose of ASTX660.
In Part 2, the primary objective is to investigate the effect of a single dose of ASTX660 on the pharmacokinetics of the CYP3A4 substrate midazolam and its metabolite, 1-hydroxy midazolam.
Safety and tolerability of a single dose of ASTX660 in the absence and presence of multiple doses of the CYP3A4 inhibitor itraconazole and in the presence of a single dose of the CYP3A4 substrate midazolam will also be evaluated.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1 | Experimental | Drug: ASTX660, Drug: ItraconazoleOral administration of ASTX660 and itraconazole at specific time points. |
| Part 2 | Experimental | Drug: ASTX660, Drug: MidazolamOral administration of ASTX660 and midazolam at specific time points. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Participant understands the study procedures and agrees to participate by providing written informed consent.
- Participant is willing and able to comply with all study procedures and restrictions.
- Participant is male aged 18 to 45 years, inclusive at Screening.
- Participant has a body mass index (BMI) ≥ 18.5 kg/m2 and ≤ 30.0 kg/m2 at Screening.
- Participant is considered medically healthy as determined by the investigator, based on clinical evaluations including medical history, physical examination, clinical laboratory tests, 12-lead electrocardiogram (ECG) in triplicate, and vital sign measurements performed at Screening.
Key exclusion criteria (28 listed)
- Participant is mentally or legally incapacitated or has significant emotional problems at the time of Screening or is expected to have such problems during the conduct of the study.
- Participant has a clinically significant medical or psychiatric condition or disease (acute or chronic) that, as judged by the investigator, would make the participant ineligible for participation in the study (eg, compromises the study data, limits the participant's ability to complete and/or participate in the study).
- Participant has a current condition or history of significant endocrine, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, urological, immunological, or neurological disorders with clinical manifestations that, as judged by the investigator, would make the participant ineligible for participation in the study.
- Participant has a chronic disease requiring medication, dietary restriction, physical therapy, and/or other routine treatment that, as judged by the investigator, would make the participant ineligible for participation in the study.
- Participant has a history of gastrointestinal (GI) surgery including but not limited to gastric resection and/or intestinal resection that resulted in a clinically significant abnormality in GI function.
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 |
|---|---|---|
| ASTX660Form: capsule; Route of administration: oral | Drug | Part 1, Part 2 |
| MidazolamForm: syrup; Route of administration: oral | Drug | Part 2 |
| ItraconazoleForm: capsule; Route of administration: oral | Drug | Part 1 |
Primary outcome
Pharmacokinetic parameter of ASTX660: Cmax
Time frame: From predose up to Day 14
Maximum plasma concentration
Pharmacokinetic parameter of ASTX660: AUC0-t
Time frame: From predose up to Day 14
Area under the plasma concentration versus time curve from time zero to the last measurable concentration
Pharmacokinetic parameter of ASTX660: AUC0-24
Time frame: From predose up to Day 14
Area under the plasma concentration versus time curve from time zero to 24 hours
Pharmacokinetic parameter of ASTX660: AUC0-inf
Time frame: From predose up to Day 14
Area under the plasma concentration versus time curve from time zero extrapolated to infinity
Pharmacokinetic parameter of midazolam and 1-hydroxyl midazolam: Cmax
Time frame: From predose up to Day 9
Maximum plasma concentration
Pharmacokinetic parameter of midazolam and 1-hydroxyl midazolam: AUC0-t
Time frame: From predose up to Day 9
Area under the plasma concentration versus time curve from time zero to the last measurable concentration
Pharmacokinetic parameter of midazolam and 1-hydroxyl midazolam: AUC0-24
Time frame: From predose up to Day 9
Area under the plasma concentration versus time curve from time zero to 24 hours
Pharmacokinetic parameter of midazolam and 1-hydroxyl midazolam: AUC0-inf
Time frame: From predose up to Day 9
Area under the plasma concentration versus time curve from time zero extrapolated to infinity
5 secondary outcomes
Pharmacokinetic parameter for ASTX660: CL/F
Time frame: From predose up to Day 14
Pharmacokinetic parameter for ASTX660: t1/2
Time frame: From predose up to Day 14
Pharmacokinetic parameter for midazolam: CL/F
Time frame: From predose up to Day 9
Pharmacokinetic parameter for midazolam: t1/2
Time frame: From predose up to Day 9
Safety: Number of participants with adverse events
Time frame: Up to Day 35
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2024.
- Individual participant dataSharing planned: No
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Screening Protocol
Pain
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 ASTX660, Midazolam and Itraconazole in people with Healthy Volunteer, run by Astex Pharmaceuticals, Inc. at 1 site in United States.
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 7 inclusion and 28 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: finished, as of the sponsor's last update on 2 Aug 2024. 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 United States. 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. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Pharmacokinetic parameter of ASTX660: Cmax (time frame: From predose up to Day 14). The study lists 8 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 2 Aug 2024.