Study in Healthy Volunteers to Investigate the Effects of Diltiazem on the Pharmacokinetics of Naloxegol

Study Overview
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Brief Summary
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Study in healthy volunteers to investigate the effects of Diltiazem on the Pharmacokinetics of naloxegol.

Detailed Description
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An Open-label, sequential, 3-period study to Assess the Effects of Diltiazem on the Pharmacokinetics of Naloxegol in Healthy Subjects

Official Title
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An Open-label, Sequential, 3-period Study to Assess the Effects of Diltiazem on the Pharmacokinetics of Naloxegol in Healthy Subjects

Conditions
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Drug Induced Constipation

Intervention / Treatment
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* Drug: Naloxegol
* Drug: Diltiazem XR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated, written informed consent prior to any study-specific procedures. Male and female (nonchildbearing potential, nonlactating) healthy volunteers aged 18 to 55 years inclusive, with suitable veins for cannulation or repeated venipuncture. Female volunteers must have negative pregnancy test (screening and admission), must not be lactating, and must be of nonchildbearing potential, confirmed at screening by being postmenopausal, or documentation of irreversible surgical sterilization not in. Male volunteers should be willing to use barrier contraception ie, condoms, from the first day of dosing until 3 months after dosing with the IP. The female partner should use contraception during this period. Volunteers must have a BMI between 18 and 30 kg/m2, inclusive, and weigh at least 50 kg. Exclusion Criteria: Any clinically significant disease or disorder (eg, cardiovascular, pulmonary, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine) which, may put the volunteer at risk of participation in the study, or influence of the ADME of drugs. Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IP. Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results as judged by the Investigator. Significant orthostatic reaction at enrolment, as judged by the Investigator. Abnormal vital signs, after 10 minutes supine rest as defined in protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Single dose naloxegol 25mg | Drug: Naloxegol<br>* Oral 25mg tablet<br>|
| Active Comparator: B<br>Diltiazem 240mg once daily day 4-6 | Drug: Diltiazem XR<br>* Oral 240mg tablet<br>|
| Active Comparator: C<br>Diltiazem 240mg once daily day 7 and 8. Single dose naloxegol 25mg day 7 | Drug: Naloxegol<br>* Oral 25mg tablet<br>Drug: Diltiazem XR<br>* Oral 240mg tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of the pharmacokinetic (PK) profile for naloxegol in terms of maximum observed plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC). |  | At predose on Days 1 and 7 and then at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of the safety profile in terms of adverse events, clinical laboratory assessments , vital signs (blood pressure and pulse rate), physical examinations, electrocardiograms, and Columbia-Suicide Severity Rating scale |  | From baseline day 1 through to Follow-up (Maximum 21 days) | 
| Description of the pharmacokinetic (PK) profile for naloxegol in terms of time to Cmax (tmax), terminal half-life (t1/2λz), terminal rate constant (λz). |  | At predose on Day 1 and 7 and then at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose | 
| Description of the pharmacokinetic (PK) profile for naloxegol in terms of area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-t)]. |  | At predose on Day 1 and 7 and then at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose | 
| Description of the pharmacokinetic (PK) profile for naloxegol in terms of area under the plasma concentration-time curve from time zero to 24hours postdose [AUC(0 24)]. |  | At predose on Day 1 and 7 and then at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose | 
| Description of the pharmacokinetic (PK) profile for naloxegol in terms of apparent oral clearance from plasma (CL/F), and apparent volume of distribution during the terminal phase (Vz/F) |  | At predose on Day 1 and 7 and then at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Healthy male and female volunteers, Drug-drug interaction, Pharmacokinetics, Naloxegol