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

Primary Purpose

Drug Induced Constipation

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Naloxegol
Diltiazem XR
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Drug Induced Constipation focused on measuring Phase 1, Healthy male and female volunteers, Drug-drug interaction, Pharmacokinetics, Naloxegol

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Active Comparator

Arm Label

A

B

C

Arm Description

Single dose naloxegol 25mg

Diltiazem 240mg once daily day 4-6

Diltiazem 240mg once daily day 7 and 8. Single dose naloxegol 25mg day 7

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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
Description of the pharmacokinetic (PK) profile for naloxegol in terms of time to Cmax (tmax), terminal half-life (t1/2λz), terminal rate constant (λz).
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)].
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)].
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)

Full Information

First Posted
May 8, 2012
Last Updated
October 13, 2014
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT01594619
Brief Title
Study in Healthy Volunteers to Investigate the Effects of Diltiazem on the Pharmacokinetics of Naloxegol
Official Title
An Open-label, Sequential, 3-period Study to Assess the Effects of Diltiazem on the Pharmacokinetics of Naloxegol in Healthy Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
May 2012 (undefined)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
August 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

5. Study Description

Brief Summary
Study in healthy volunteers to investigate the effects of Diltiazem on the Pharmacokinetics of naloxegol.
Detailed Description
An Open-label, sequential, 3-period study to Assess the Effects of Diltiazem on the Pharmacokinetics of Naloxegol in Healthy Subjects

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Drug Induced Constipation
Keywords
Phase 1, Healthy male and female volunteers, Drug-drug interaction, Pharmacokinetics, Naloxegol

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
44 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Experimental
Arm Description
Single dose naloxegol 25mg
Arm Title
B
Arm Type
Active Comparator
Arm Description
Diltiazem 240mg once daily day 4-6
Arm Title
C
Arm Type
Active Comparator
Arm Description
Diltiazem 240mg once daily day 7 and 8. Single dose naloxegol 25mg day 7
Intervention Type
Drug
Intervention Name(s)
Naloxegol
Intervention Description
Oral 25mg tablet
Intervention Type
Drug
Intervention Name(s)
Diltiazem XR
Intervention Description
Oral 240mg tablet
Primary Outcome Measure Information:
Title
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).
Time Frame
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 Measure Information:
Title
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
Time Frame
From baseline day 1 through to Follow-up (Maximum 21 days)
Title
Description of the pharmacokinetic (PK) profile for naloxegol in terms of time to Cmax (tmax), terminal half-life (t1/2λz), terminal rate constant (λz).
Time Frame
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
Title
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)].
Time Frame
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
Title
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)].
Time Frame
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
Title
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)
Time Frame
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bo Fransson, MD
Organizational Affiliation
AstraZeneca, Sodertalje Sweden
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Dave Matthews, MD
Organizational Affiliation
Quintiles, Inc Kansas Overland Park US
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mark Sostek, MD
Organizational Affiliation
AstraZeneca, Wilmington US
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Overland Park
State/Province
Kansas
Country
United States

12. IPD Sharing Statement

Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=1401&filename=Clinical_Study_Report_Synopsis_D3820C00032.pdf
Description
Clinical_Study_Report_Synopsis_D3820C00032

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

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