Clinical trial NCT03126578: Open-label, Single Center, Non-randomized, Fixed Sequence Phase 1 Drug-drug Interaction Study With LEO 32731 and Midazolam
Official title: Open-label, Single Center, Non-randomized, Fixed Sequence Phase 1 Drug-drug Interaction Study With LEO 32731 and Midazolam
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Drug Interaction Potentiation
Lead sponsor: LEO Pharma
Sponsor class: INDUSTRY
First posted: 2017-04-24
Enrollment: 32
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

The study will be conducted in two seamless parts:

Part I - Maximal Tolerated Dose (MTD) Part II - Drug-Drug Interaction with midazolam


Eligibility criteria: Inclusion Criteria:

1. 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.
2. Subjects will be males between 18 and 55 years of age, inclusive.
3. Subjects will have a body mass index (BMI) between 18.0 and 30.0 kg/m2 inclusive.
4. Subjects must be in good health, as determined by medical history, physical examination, vital signs assessment, 12-lead ECG, and clinical laboratory evaluations.
5. 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.
6. 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.

Exclusion Criteria:

1. 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.
2. 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).
3. 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.
4. 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.
5. 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.

Primary outcomes:
measure: Pharmacokinetic (PK) parameters of midazolam AUC0-t
timeFrame: Day -1 and Day 17
measure: Pharmacokinetic (PK) parameters of midazolam Cmax
timeFrame: Day -1 and Day 17
Secondary outcomes:
measure: AUC0-t midazolam
timeFrame: Day 4 and Day 7
measure: AUC0-inf of midazolam
timeFrame: Day 4 and Day 7
measure: Cmax of midazolam
timeFrame: Day 4 and Day 7
measure: AUC0-inf of midazolam
timeFrame: Day -1 and Day 17
measure: Tmax of midazolam
timeFrame: Day -1 and Day 17
measure: t1/2 of midazolam
timeFrame: Day -1 and Day 17
measure: CL/F of midazolam
timeFrame: Day -1 and Day 17
measure: Vz/F of midazolam
timeFrame: Day -1 and Day 17
Other outcomes:
Locations:
city: Neu-Ulm
country: Germany
facility: Nuvisan GmbH
Study officials:
affiliation: Nuvisan GmbH
name: Manuela Koch, MD
role: PRINCIPAL_INVESTIGATOR
References: