Drug Interaction PotentiationPhase 1NCT03126578
Open-label, Single Center, Non-randomized, Fixed Sequence Phase 1 Drug-drug Interaction Study With LEO 32731 and Midazolam
A Phase 1 study testing LEO 32731 and Midazolam in people with Drug Interaction Potentiation, run by LEO Pharma at 1 site in Germany.
Trial summary
This is a single center, non-randomized, open-label, fixed sequence study to investigate the effect of multiple oral dosing of LEO 32731 (up-titrated), on CYP3A activity in healthy male subjects using midazolam as a probe CYP3A substrate. Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Drug Interaction Potentiation
- What is being tested?
- LEO 32731 and Midazolam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteGermany
- Study dates
- 31 May 2017to 20 Oct 2017
- 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
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects will, prior to any study related activities, have given their written informed consent to participate in the study and to abide by the study restrictions.
- Subjects will be males between 18 and 55 years of age, inclusive.
- Subjects will have a body mass index (BMI) between 18.0 and 30.0 kg/m2 inclusive.
- Subjects must be in good health, as determined by medical history, physical examination, vital signs assessment, 12-lead ECG, and clinical laboratory evaluations.
- Subjects (including those who have had a vasectomy) must agree to use condoms with spermicide during each sexual intercourse or must agree to be abstinent starting at first drug administration until 3 month after the final dosing.
- Also subjects must agree not to donate sperm in the same time period.
- Subjects' female partner of childbearing potential must use an additional acceptable method of contraception. Eligible methods are: hormonal contraceptives (oral, injected, implanted, transdermal), intrauterine devices or systems (e.g. hormonal and non-hormonal IUD), barrier methods (condom and diaphragm, condom and cervical cap, etc.) in combination with a spermicide.
Who cannot join
- Subjects who have received any prescribed systemic or topical medication within 14 days of the first dose administration unless in the opinion of the Investigator the medication will not interfere with the study procedures or compromise safety.
- Subjects who have used any non-prescribed systemic or topical medication (including herbal remedies) within 7 days of the first dose administration (excluding occasional use of paracetamol or ibuprofen, e.g. in case of pain).
- Subjects who have received any medications, including St John's Wort known to alter drug absorption or elimination processes (change the enzyme levels) within 30 days of the first dose administration of study drug.
- Subjects who are still participating in a clinical study (e.g. attending follow-up visits) or who have participated in a clinical study involving administration of an investigational drug with new chemical entity within the past 60 days, or a marketed drug compound within the past 30 days prior to the first dosing.
- Subjects who have donated any blood, plasma or platelets in 3 months prior to first dosing or who have made donations on more than 3 occasions within the 12 months preceding the first dose administration.
Trial locations and contacts
1 site in 1 country.
About this study
This is a single center, non-randomized, open-label, fixed sequence study to investigate the effect of multiple oral dosing of LEO 32731 (up-titrated), on CYP3A activity in healthy male subjects using midazolam as a probe CYP3A substrate.
The study will be conducted in two seamless parts:
Part I - Maximal Tolerated Dose (MTD) Part II - Drug-Drug Interaction with midazolam
- Conditions
- Drug Interaction Potentiation
- Being tested
- LEO 32731, Midazolam
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LEO 32731Drug
LEO 32731 is being developed by LEO Pharma.
MidazolamDrug
Benzodiazepine
| Study group | Role | What they receive |
|---|---|---|
| All subjects | Experimental | Part I - Maximum Tolerated Dose: All subjects will receive oral doses of LEO 32731 up-titrated from 10 mg bid on Days 1-3, 20 mg bid on Days 4-6 and 40 mg bid on Days 7-12.
Part II - Drug-Drug Interaction: All subjects will receive oral doses of LEO 32731 in dose schedule decided upon data from Part I. Subjects will receive a single oral dose of 2.5 mg midazolam on Day -1 prior to the first dose of LEO 32731 and on Days 4, 7 and 17 of multiple dosing with LEO 32731. Receives: Drug: LEO 32731; Drug: Midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic (PK) parameters of midazolam AUC0-t
PK parameters AUC0-t will be analyzed on Day -1 and Day 17.
Measured: Day -1 and Day 17
Pharmacokinetic (PK) parameters of midazolam Cmax
PK parameter Cmax will be analyzed on Day -1 and Day 17.
Measured: Day -1 and Day 17
Secondary outcomes (8)
AUC0-t midazolam
PK parameters of midazolam on Day 4 and Day 7 will only be calculated if relevant differences are seen in midazolam PK parameters between Day -1 and Day 17.
Measured: Day 4 and Day 7
AUC0-inf of midazolam
PK parameters of midazolam on Day 4 and Day 7 will only be calculated if relevant differences are seen in midazolam PK parameters between Day -1 and Day 17.
Measured: Day 4 and Day 7
Cmax of midazolam
PK parameters of midazolam on Day 4 and Day 7 will only be calculated if relevant differences are seen in midazolam PK parameters between Day -1 and Day 17.
Measured: Day 4 and Day 7
AUC0-inf of midazolam
Further PK parameters (AUC0-inf, tmax, t1/2, CL/F and Vz/F) of midazolam on Days -1 and 17 (if applicable these parameters will be calculated on Day 4 and Day 7, too).
Measured: Day -1 and Day 17
Tmax of midazolam
Further PK parameters (AUC0-inf, tmax, t1/2, CL/F and Vz/F) of midazolam on Days -1 and 17 (if applicable these parameters will be calculated on Day 4 and Day 7, too).
Measured: Day -1 and Day 17
t1/2 of midazolam
Further PK parameters (AUC0-inf, tmax, t1/2, CL/F and Vz/F) of midazolam on Days -1 and 17 (if applicable these parameters will be calculated on Day 4 and Day 7, too).
Measured: Day -1 and Day 17
CL/F of midazolam
Further PK parameters (AUC0-inf, tmax, t1/2, CL/F and Vz/F) of midazolam on Days -1 and 17 (if applicable these parameters will be calculated on Day 4 and Day 7, too).
Measured: Day -1 and Day 17
Vz/F of midazolam
Further PK parameters (AUC0-inf, tmax, t1/2, CL/F and Vz/F) of midazolam on Days -1 and 17 (if applicable these parameters will be calculated on Day 4 and Day 7, too).
Measured: Day -1 and Day 17
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2017
- Study start31 May 2017
- Primary completion20 Oct 2017
- Study completion20 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug Interaction PotentiationStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- LEO Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Manuela Koch, MD, Principal investigator, Nuvisan GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03126578
- Sponsor's protocol ID
- LP0058-1324
- Other IDs
- 2016-003882-24, 2016
- Status last verified
- Jun 2017
- First submitted
- 12 Apr 2017
- Last updated
- 14 Nov 2017
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Single Center, Non-randomized, Fixed Sequence Phase 1 Drug-drug Interaction Study With LEO 32731 and Midazolam
- ClinicalTrials.gov ID
- NCT03126578
- Acronym / sponsor ID
- LP0058-1324
- Conditions
- Drug Interaction Potentiation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- LEO PharmaIndustry (pharma, biotech, devices)
- Study start
- 31 May 2017 (actual)
- Primary completion
- 20 Oct 2017 (actual)
- Study completion
- 20 Oct 2017 (actual)
- First posted
- 24 Apr 2017 (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 is a single center, non-randomized, open-label, fixed sequence study to investigate the effect of multiple oral dosing of LEO 32731 (up-titrated), on CYP3A activity in healthy male subjects using midazolam as a probe CYP3A substrate.
The study will be conducted in two seamless parts:
Part I - Maximal Tolerated Dose (MTD) Part II - Drug-Drug Interaction with midazolam
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All subjects | Experimental | Drug: LEO 32731, Drug: MidazolamPart I - Maximum Tolerated Dose: All subjects will receive oral doses of LEO 32731 up-titrated from 10 mg bid on Days 1-3, 20 mg bid on Days 4-6 and 40 mg bid on Days 7-12. Part II - Drug-Drug Interaction: All subjects will receive oral doses of LEO 32731 in dose schedule decided upon data from Part I. Subjects will receive a single oral dose of 2.5 mg midazolam on Day -1 prior to the first dose of LEO 32731 and on Days 4, 7 and 17 of multiple dosing with LEO 32731. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Subjects will, prior to any study related activities, have given their written informed consent to participate in the study and to abide by the study restrictions.
- Subjects will be males between 18 and 55 years of age, inclusive.
- Subjects will have a body mass index (BMI) between 18.0 and 30.0 kg/m2 inclusive.
- Subjects must be in good health, as determined by medical history, physical examination, vital signs assessment, 12-lead ECG, and clinical laboratory evaluations.
- Subjects (including those who have had a vasectomy) must agree to use condoms with spermicide during each sexual intercourse or must agree to be abstinent starting at first drug administration until 3 month after the final dosing.
Key exclusion criteria (5 listed)
- Subjects who have received any prescribed systemic or topical medication within 14 days of the first dose administration unless in the opinion of the Investigator the medication will not interfere with the study procedures or compromise safety.
- Subjects who have used any non-prescribed systemic or topical medication (including herbal remedies) within 7 days of the first dose administration (excluding occasional use of paracetamol or ibuprofen, e.g. in case of pain).
- Subjects who have received any medications, including St John's Wort known to alter drug absorption or elimination processes (change the enzyme levels) within 30 days of the first dose administration of study drug.
- Subjects who are still participating in a clinical study (e.g. attending follow-up visits) or who have participated in a clinical study involving administration of an investigational drug with new chemical entity within the past 60 days, or a marketed drug compound within the past 30 days prior to the first dosing.
- Subjects who have donated any blood, plasma or platelets in 3 months prior to first dosing or who have made donations on more than 3 occasions within the 12 months preceding the first dose administration.
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 |
|---|---|---|
| LEO 32731LEO 32731 is being developed by LEO Pharma. | Drug | All subjects |
| MidazolamBenzodiazepine | Drug | All subjects |
Primary outcome
Pharmacokinetic (PK) parameters of midazolam AUC0-t
Time frame: Day -1 and Day 17
PK parameters AUC0-t will be analyzed on Day -1 and Day 17.
Pharmacokinetic (PK) parameters of midazolam Cmax
Time frame: Day -1 and Day 17
PK parameter Cmax will be analyzed on Day -1 and Day 17.
8 secondary outcomes
AUC0-t midazolam
Time frame: Day 4 and Day 7
AUC0-inf of midazolam
Time frame: Day 4 and Day 7
Cmax of midazolam
Time frame: Day 4 and Day 7
AUC0-inf of midazolam
Time frame: Day -1 and Day 17
Tmax of midazolam
Time frame: Day -1 and Day 17
t1/2 of midazolam
Time frame: Day -1 and Day 17
CL/F of midazolam
Time frame: Day -1 and Day 17
Vz/F of midazolam
Time frame: Day -1 and Day 17
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 14 Nov 2017.
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.
Manuela Koch, MD principal investigator
Nuvisan GmbH
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 LEO 32731 and Midazolam in people with Drug Interaction Potentiation, run by LEO Pharma at 1 site in Germany.
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 5 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 14 Nov 2017. 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 Germany. 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 (PK) parameters of midazolam AUC0-t (time frame: Day -1 and Day 17). The study lists 2 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 14 Nov 2017.