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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01594619
First received: May 8, 2012
Last updated: October 13, 2014
Last verified: October 2014
  Purpose

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


Condition Intervention Phase
Drug Induced Constipation
Drug: Naloxegol
Drug: Diltiazem XR
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: An Open-label, Sequential, 3-period Study to Assess the Effects of Diltiazem on the Pharmacokinetics of Naloxegol in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

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). [ 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 ] [ Designated as safety issue: No ]

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 [ Time Frame: From baseline day 1 through to Follow-up (Maximum 21 days) ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 44
Study Start Date: May 2012
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Single dose naloxegol 25mg
Drug: Naloxegol
Oral 25mg tablet
Active Comparator: B
Diltiazem 240mg once daily day 4-6
Drug: Diltiazem XR
Oral 240mg tablet
Active Comparator: C
Diltiazem 240mg once daily day 7 and 8. Single dose naloxegol 25mg day 7
Drug: Naloxegol
Oral 25mg tablet
Drug: Diltiazem XR
Oral 240mg tablet

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01594619

Locations
United States, Kansas
Research Site
Overland Park, Kansas, United States
Sponsors and Collaborators
AstraZeneca
Investigators
Study Chair: Bo Fransson, MD AstraZeneca, Sodertalje Sweden
Principal Investigator: Dave Matthews, MD Quintiles, Inc Kansas Overland Park US
Study Director: Mark Sostek, MD AstraZeneca, Wilmington US
  More Information

Additional Information:
No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01594619     History of Changes
Other Study ID Numbers: D3820C00032
Study First Received: May 8, 2012
Last Updated: October 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Phase 1
Healthy male and female volunteers
Drug-drug interaction
Pharmacokinetics
Naloxegol

Additional relevant MeSH terms:
Constipation
Signs and Symptoms
Signs and Symptoms, Digestive
Diltiazem
Antihypertensive Agents
Calcium Channel Blockers
Cardiovascular Agents
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on November 20, 2014