The Pharmacokinetic Interaction Between Oral Casopitant and Oral Dolasetron, Granisetron or Rosiglitazone in Subjects

NCT ID: NCT00511823

Last Updated: 2017-08-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-23
• Study Completion Date: 2007-09-21

Brief Summary

This A Three-Part Drug-Drug Interaction Study To Evaluate Effects of Casopitant On Dolasetron, Granisetron or Rosiglitazone When Co-Administered in Healthy Adults

Conditions

Nausea and Vomiting, Chemotherapy-Induced

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Subjects in Part A

Subjects will receive 100 milligrams (mg) of oral dolasetron once daily for 3 days during treatment period 1. In treatment period 2, subjects will receive 100 mg oral dolasetron once daily on days 1, 2 and 3 along with 150 mg oral casopitant on day 1 and 50 mg oral casopitant on days 2 and 3. The treatment periods will be separated by will be separated by a 5 - 14 day wash-out period.

Group Type: EXPERIMENTAL

casopitant

Intervention Type: DRUG

The doses of casopitant will be comprised of 150 mg (one 150 mg tablet) and 50 mg (one 50 mg tablet). Casopitant will be taken with 240 milliliters (mL) of water on an empty stomach following at least 2 hour fast.

dolasetron

Intervention Type: DRUG

The dose of oral dolasetron will be comprised of 100 mg (one 100 mg tablet or two 50 mg tablets). Dolasetron will be taken with 240 mL of water on an empty stomach following at least 2 hour fast.

Subjects in Part B

Subjects will receive 2 mg of oral granisetron once daily for 3 days during treatment period 1. In treatment period 2, subjects will receive 2 mg oral granisetron once daily on days 1, 2 and 3 along with 150 mg oral casopitant once daily on day 1 and 50 mg oral casopitant once daily on days 2 and 3. The treatment periods will be separated by will be separated by a 5 - 14 day wash-out period.

Group Type: EXPERIMENTAL

casopitant

Intervention Type: DRUG

The doses of casopitant will be comprised of 150 mg (one 150 mg tablet) and 50 mg (one 50 mg tablet). Casopitant will be taken with 240 milliliters (mL) of water on an empty stomach following at least 2 hour fast.

granisetron

Intervention Type: DRUG

The dose of oral granisetron will be comprised of 2 mg (two 1 mg tablets). Granisetron will be taken with 240 mL of water on an empty stomach following at least 2 hour fast.

Subjects in Part C

Subjects will receive 4 mg of oral rosiglitazone once daily for 3 days during treatment period 1. In treatment period 2, subjects will receive 4 mg oral rosiglitazone once daily on days 1, 2 and 3 along with 150 mg oral casopitant once daily on day 1 and 50 mg oral casopitant once daily on days 2 and 3. The treatment periods will be separated by will be separated by a 5 - 14 day wash-out period.

Group Type: EXPERIMENTAL

casopitant

Intervention Type: DRUG

The doses of casopitant will be comprised of 150 mg (one 150 mg tablet) and 50 mg (one 50 mg tablet). Casopitant will be taken with 240 milliliters (mL) of water on an empty stomach following at least 2 hour fast.

rosiglitazone

Intervention Type: DRUG

The dose of oral rosiglitazone will be comprised of 4 mg (two 2 mg tablets or one 4 mg tablet). Rosiglitazone will be taken with 240 mL of water on an empty stomach following at least 2 hour fast.

Interventions

casopitant

The doses of casopitant will be comprised of 150 mg (one 150 mg tablet) and 50 mg (one 50 mg tablet). Casopitant will be taken with 240 milliliters (mL) of water on an empty stomach following at least 2 hour fast.

Intervention Type: DRUG

dolasetron

The dose of oral dolasetron will be comprised of 100 mg (one 100 mg tablet or two 50 mg tablets). Dolasetron will be taken with 240 mL of water on an empty stomach following at least 2 hour fast.

Intervention Type: DRUG

granisetron

The dose of oral granisetron will be comprised of 2 mg (two 1 mg tablets). Granisetron will be taken with 240 mL of water on an empty stomach following at least 2 hour fast.

Intervention Type: DRUG

rosiglitazone

The dose of oral rosiglitazone will be comprised of 4 mg (two 2 mg tablets or one 4 mg tablet). Rosiglitazone will be taken with 240 mL of water on an empty stomach following at least 2 hour fast.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• An adult healthy male or female.
• Age: 18 to 64 years, inclusive.
• Body mass index (BMI) = 19 to = 37 kg/m2.
• A female if she is of Non-childbearing potential, OR
• A female who has a negative serum pregnancy test within 14 days prior to the first dose of study medication and agrees to use adequate contraception during the study and for 14 days after the last dose of study medication.
• Adequate organ systems function [Hemoglobin is within normal limits ± 10%; Platelets is = 100 X 109/L or = lower limit of normal (LLN); Aspartate aminotransaminase = Upper limit of normal (ULN); Total bilirubin = 1.2 times ULN; Creatine phosphokinase < 1.5 times ULN; Renal Calculated creatinine clearance = 50 mL/min]
• Able to swallow and retain oral medication.
• Able to understand and comply with the requirements, instruction and restrictions stated in the informed consent.
• Signed and dated informed consent.

Exclusion Criteria

• Clinically relevant abnormality, including any degree of heart failure or clinically significant cardiac disease, identified on the screening exam or any other medical condition or circumstance making the subject unsuitable for participation in the study.
• For Part A (dolasetron-casopitant drug-drug interaction), any subject who exhibits gene duplication for CYP2D6.
• History of drug or other allergy which, in the opinion of the Investigator, contraindicates participation.
• Known immediate hypersensitivity reaction or idiosyncrasy to study drugs or any drug chemically related to the study medications.
• Use of an investigational drug within 28 days or 5 half-lives, whichever is longer, preceding the first dose of study medication(s).
• Blood donation in excess of 500 mL within 56 days prior to dosing or intends to donate within 30 days of the post-treatment follow-up visit.
• Presence of or suspected iron deficiency.
• Stool positive for occult blood.
• Troponin I level above 10% of the coefficient of variation of the assay.
• For female subjects of childbearing potential, a positive serum pregnancy test.
• Female subject who is lactating.
• Positive urine drug screen (UDS) including alcohol.
• Positive for HIV antibody, hepatitis C antibody or hepatitis B surface antigen (HBsAg).
• Positive urinary cotinine.
• Smoking history of = 4 packs per day/year or smoked more than 2 times within the past 30 days prior to screening.
• History of drug abuse or dependence within 6 months of screening.
• History of alcohol abuse within 6 months of screening or alcohol consumption in the past 6 months exceeding 7 drinks/week for women and 14 drinks/week for men (where 1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor).
• Presence of an active infection.
• Corrected QT interval (QTc) > 450 msecs.
• Pepsinogen level below the lower limit of laboratory reference range (LLRR).
• Active peptic ulcer disease (PUD) or a history of PUD of unknown etiology.
• Use of any prescription or non-prescription drug(s), including oral contraceptives, herbal or dietary supplements or vitamins within 14 days, or 5 half-lives (whichever is longer) prior to the first dose of study medication.
• Consumption of food or drink containing grapefruit or grapefruit juice, apple juice, Seville oranges, kumquats, pomelos, star fruit, red wine, charbroiled meats, cabbage or vegetables from the mustard green family (e.g., kale, broccoli, watercress, collard greens, kohlrabi, brussels sprouts, mustard) within 7 days prior to the first dose of study medication(s).
• History of cholecystectomy or biliary tract disease.
• Any serious or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Evansville, Indiana, United States

Countries

United States

References

Adams LM, Johnson B, Zhang K, Yue L, Kirby LC, Lebowitz P, Stoltz R. Effect of casopitant, a novel NK-1 antagonist, on the pharmacokinetics of dolasetron and granisetron. Support Care Cancer. 2009 Sep;17(9):1187-93. doi: 10.1007/s00520-008-0572-4. Epub 2009 Feb 10.

Reference Type: RESULT

PMID: 19205754 (View on PubMed)

Study Documents

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

https://www.clinicalstudydatarequest.com

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Other Identifiers

NKV110483

Identifier Type: -

Identifier Source: org_study_id