Study in Healthy Volunteers to Investigate the Effects of Diltiazem on the Pharmacokinetics of Naloxegol - Full Text View

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:

MedlinePlus related topics: Constipation

Drug Information available for: Verapamil hydrochloride Diltiazem hydrochloride Diltiazem Diltiazem malate

U.S. FDA Resources

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

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

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:	November 21, 2012
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, Digestive
Signs and Symptoms
Diltiazem
Verapamil
Calcium Channel Blockers
Membrane Transport Modulators

Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents
Vasodilator Agents
Anti-Arrhythmia Agents

ClinicalTrials.gov processed this record on May 19, 2013