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

NCT01594619 | Completed Phase 1

• 1 other identifier: D3820C00032
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Drug Induced Constipation

Keywords

Phase 1; Healthy male and female volunteers; Drug-drug interaction; Pharmacokinetics; Naloxegol

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

Study Arms (3)

A

EXPERIMENTAL

Single dose naloxegol 25mg

Drug: Naloxegol

B

ACTIVE COMPARATOR

Diltiazem 240mg once daily day 4-6

Drug: Diltiazem XR

C

ACTIVE COMPARATOR

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

Drug: Naloxegol; Drug: Diltiazem XR

Interventions

Naloxegol DRUG

Oral 25mg tablet

A; C

Diltiazem XR DRUG

Oral 240mg tablet

B; C

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Overland Park, Kansas, United States

Location

Related Links

• Clinical\_Study\_Report\_Synopsis\_D3820C00032

MeSH Terms

Interventions

naloxegol; Diltiazem

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Bo Fransson, MD

  AstraZeneca, Sodertalje Sweden

  STUDY CHAIR

• Dave Matthews, MD

  Quintiles, Inc Kansas Overland Park US

  PRINCIPAL INVESTIGATOR

• Mark Sostek, MD

  AstraZeneca, Wilmington US

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2012
• First Posted: May 9, 2012
• Study Start: May 1, 2012
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: October 15, 2014

Record last verified: 2014-10

Locations

US (1)