A Study to Investigate the Effect of Itraconazole on the Pharmacokinetics of Debio 1450 in Healthy Subjects

• ClinicalTrials.gov Identifier: NCT03209648
• Recruitment Status: Completed
• First Posted: July 6, 2017
• Last Update Posted: October 18, 2017
• Sponsor: Debiopharm International SA
• Information provided by (Responsible Party): Debiopharm International SA

Study Description

Brief Summary:

Debio 1450 is metabolised mainly by CYP3A4, therefore inhibitors of CYP3A4 have the potential to raise Debio 1450 plasma concentrations. Hence, it is important to determine the effect of CYP3A4 inhibition by itraconazole on the Pharmacokinetics of Debio 1450.

Condition or disease	Intervention/treatment	Phase
Healthy Participants	Drug: Debio 1450; Drug: Itraconazole	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Open-Label, Fixed Sequence Study to Investigate the Effect of Itraconazole on the Pharmacokinetics of Debio 1450 in Healthy Subjects
• Actual Study Start Date: June 14, 2017
• Actual Primary Completion Date: August 23, 2017
• Actual Study Completion Date: August 31, 2017

Arms and Interventions

Arm

Intervention/treatment

Experimental: Debio 1450; In Treatment Period 1, participants will receive single oral dose of Debio 1450 40 mg on Day 1. In Treatment Period 2, participants will receive itraconazole 200 mg, twice daily (BID) orally, on Day 1, followed by itraconazole 200 mg once daily (QD), on Days 2 to 4, and then single oral dose of Debio 1450 40 mg and itraconazole 200 mg on Day 5, followed by a single oral dose of itraconazole 200 mg on Days 6 and 7.

Drug: Debio 1450; Debio 1450, 40 mg capsule.; Drug: Itraconazole; Itraconazole, 20 mL of 10 mg/mL solution.

Outcome Measures

Primary Outcome Measures :

1. Maximum Observed Plasma Concentration (Cmax) of Debio 1452 [ Time Frame: Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose ]
2. Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUC0-∞) of Debio 1452 [ Time Frame: Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose ]
3. Area Under the Plasma Concentration-time Curve from Time Zero to Time (t) (AUC0-t) of Debio 1452 [ Time Frame: Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose ]

Secondary Outcome Measures :

1. Area Under the Plasma Concentration-time Curve from Time Zero to 12 Hours Postdose (AUC0-12) of Debio 1452, Debio 1450, Debio 1452-M1, and desmethyl Debio 1452 [ Time Frame: Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose ]
2. Time to Reach Maximum Concentration (Tmax) of Debio 1452, Debio 1450, Debio 1452-M1, desmethyl Debio 1452 and Itraconazole [ Time Frame: Debio 1450 and its metabolites: Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose. Itraconazole: Days 1, 3, and 6: predose, Days 4 and 5: predose, and 0.5, 1, 2, 3, 4, 6, 8, 12 hours postdose ]
3. Apparent Plasma Terminal Elimination Half-life (t1/2) of Debio 1452, Debio 1450, Debio 1452-M1, desmethyl Debio 1452 and Itraconazole [ Time Frame: Debio 1450 and its metabolites: Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose. Itraconazole: Days 1, 3, and 6: predose, Days 4 and 5: predose, and 0.5, 1, 2, 3, 4, 6, 8, 12 hours postdose ]
4. Mean Residence Time (MRT) of Debio 1452, Debio 1450, Debio 1452-M1, and desmethyl Debio 1452 [ Time Frame: Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose ]
   the mean residence time is the average time the drug stays at the site of action.
5. Apparent Total Body Clearance of a Drug from the Plasma (CL/F) of Debio 1452 [ Time Frame: Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose ]
   Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
6. Apparent Volume of Distribution During the Terminal (lamdaz) Phase (Vz/F) of Debio 1452 [ Time Frame: Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose ]
   Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug.
7. Maximum Observed Plasma Concentration (Cmax) of Debio 1450, Debio 1452-M1, desmethyl Debio 1452 and Itraconazole [ Time Frame: Debio 1450 and its metabolites: Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose. Itraconazole: Days 1, 3, and 6: predose, Days 4 and 5: predose, and 0.5, 1, 2, 3, 4, 6, 8, 12 hours postdose ]
8. Area Under the Plasma Concentration-time Curve from Time Zero to Time (t) (AUC0-t) of Debio 1450, Debio 1452-M1 and desmethyl Debio 1452 [ Time Frame: Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose ]
9. Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUC0-infinity) of Debio 1450, Debio 1452-M1 and desmethyl Debio 1452 [ Time Frame: Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose ]
10. Metabolite:Parent Cmax Ratio (for Debio 1452-M1 and desmethyl Debio 1452 only; Debio 1452 as Parent; Based on Molar Data) [ Time Frame: Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose ]
11. Metabolite:Parent AUC ratio (for Debio 1452-M1 and desmethyl Debio 1452 only; Debio 1452 as Parent; Based on Molar Data) [ Time Frame: Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose ]
12. Area Under the Plasma Concentration-time Curve During a Dosing Interval at Steady State (AUC0-τ) of Itraconazole [ Time Frame: Days 1, 3, and 6: predose Days 4 and 5: predose, and 0.5, 1, 2, 3, 4, 6, 8, 12 hours postdose ]
13. Measured Concentration at the end of a Dosing Interval at Steady State (Ctrough) of Itraconazole [ Time Frame: Days 1, 3, and 6: predose Days 4 and 5: predose, and 0.5, 1, 2, 3, 4, 6, 8, 12 hours postdose ]
14. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Week 7 ]
    An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Meets protocol-specified criteria for qualification and contraception.
• Is willing and able to comply with restrictions related to food, drink and medications.
• Voluntarily consents to participate and provides written informed consent prior to any protocol-specific procedures.

Exclusion Criteria:

• Has history or current use of over-the-counter medications, dietary supplements, or drugs (including nicotine and alcohol) outside protocol-specified parameters.

• Has signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise:

  • the safety or well-being of the participant or study staff.
  • the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding); the analysis of results.

Contacts and Locations

Locations

United Kingdom

Covance Clinical Research Unit Ltd.

Leeds, United Kingdom, LS2 9LH

Sponsors and Collaborators

Debiopharm International SA

More Information

• Responsible Party: Debiopharm International SA
• ClinicalTrials.gov Identifier: NCT03209648
• Other Study ID Numbers: Debio 1450-111; 2017-001352-60 ( EudraCT Number )
• First Posted: July 6, 2017
• Last Update Posted: October 18, 2017
• Last Verified: October 2017

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Itraconazole; Antifungal Agents; Anti-Infective Agents; 14-alpha Demethylase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Steroid Synthesis Inhibitors; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Cytochrome P-450 CYP3A Inhibitors