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

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

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

Study Overview

• Status: Completed
• Conditions: Drug Induced Constipation
• Intervention / Treatment: Drug: Naloxegol; Drug: Diltiazem XR

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Dave Matthews, MD, Quintiles, Inc Kansas Overland Park US

Publications and helpful links

Helpful Links

• Clinical_Study_Report_Synopsis_D3820C00032

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (ACTUAL): August 1, 2012
• Study Completion (ACTUAL): August 1, 2012

Study Registration Dates

• First Submitted: May 8, 2012
• First Submitted That Met QC Criteria: May 8, 2012
• First Posted (ESTIMATE): May 9, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): October 15, 2014
• Last Update Submitted That Met QC Criteria: October 13, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Phase 1; Naloxegol; Drug-drug interaction; Healthy male and female volunteers
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Peripheral Nervous System Agents; Sensory System Agents; Membrane Transport Modulators; Narcotic Antagonists; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Naloxegol; Diltiazem
• Other Study ID Numbers: D3820C00032