Study in Healthy Volunteers to Investigate the Effects of Quinidine on the Pharmacokinetics of NKTR-118

Drug Induced Constipation Clinical Trial

Official title:

A Randomized, 2-Part, Crossover, Single Center Study to Evaluate Effect of Quinidine on the Pharmacokinetics of NKTR-118 and the Concomitant Effect of Quinidine and NKTR-118 on Morphine-induced Miosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01533155
• Other study ID #: D3820C00011
• Status: Completed
• Phase: Phase 1
• First received: February 10, 2012
• Last updated: October 13, 2014
• Start date: March 2012
• Est. completion date: September 2012

Study information

• Verified date: October 2014
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Study in healthy volunteers to investigate the effects of Quinidine on the Pharmacokinetics of NKTR-118

Description:

A Randomized, 2-Part, Crossover, Single Center Study to Evaluate Effect of Quinidine on the Pharmacokinetics of NKTR-118 and the Concomitant Effect of Quinidine and NKTR-118 on Morphine-induced Miosis

Recruitment information / eligibility

• Status: Completed
• Enrollment: 214
• Est. completion date: September 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 be nonpregnant and nonlactating. Women of childbearing potential must have negative pregnancy test (screening and admission) and be using a highly-effective form of birth control for 3 months before enrollment.

• 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.

• History (personal or family) of torsades de pointes, any other polymorphic ventricular tachycardia, long QT syndrome, sudden death or Brugada syndrome, or personal history of sustained (greater than 30 s) monomorphic ventricular tachycardia.

• Abnormal vital signs, after 10 minutes supine rest as defined in protocol.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Constipation
• Drug Induced Constipation

Intervention

Drug:
• Nektar 118
Oral 25 mg tablet
• Quinidine
Oral 200 mg tablet
• Quinidine placebo
Oral Tablet
• Morphine
10 mg/ml, intravenously

Locations

Country	Name	City	State
United States	Research Site	Overland Park	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Description of the pharmacokinetic (PK) profile for NKTR- 118 in terms of maximum observed plasma concentration (Cmax), time to Cmax (tmax), apparent terminal half-life (t1/2?z).		At predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose.	No
Primary	Description of the PK profile for NKTR- 118 in terms of apparent terminal rate constant (?z), area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC).		At predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose.	No
Primary	Description of the PK profile for NKTR 118 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 and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose.	No
Primary	Description of the PK profile for NKTR 118 in terms of area under the plasma concentration-time curve from time zero to 24 hours [AUC(0-24)].		At predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose.	No
Primary	Description of the PK profile for NKTR 118 in terms of apparent oral clearance from plasma (CL/F), and apparent volume of distribution during the terminal phase (Vz/F).		At predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose.	No
Secondary	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 up to 21 days.	Yes
Secondary	Description of results from pupillary measurements in terms of size change from baseline on both eyes in mm. (Measurements in 4 different conditions: dark, 0.04 lux, 0.4 lux and 4 lux)		Measurments from baseline day -1, and at 0.5, 1, 2, 3, 4, 6, and 24 hours post dose.	No

External Links

•   Clinical_Study_Report_Synopsis_D3820C00011