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

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

Study Description
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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
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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

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Arms and Interventions
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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
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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
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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
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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03209648


Locations
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United Kingdom
Covance Clinical Research Unit Ltd.
Leeds, United Kingdom, LS2 9LH
Sponsors and Collaborators
Debiopharm International SA
More Information
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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    Key Record Dates
Last Update Posted: October 18, 2017
Last Verified: October 2017

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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