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

NCT00511823 | Completed Phase 1

• 1 other identifier: NKV110483
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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

Keywords

drug-drug interaction,; rosiglitazone,; safety; CYP2C8,; pharmacokinetics,; CYP3A4,; granisetron,; dolasetron,; CYP2D6,; casopitant,

Outcome Measures

Primary Outcomes (1)

• Change of AUC and Cmax of dolasetron, granisetron and rosiglitazone after oral administration alone and co-administered with oral casopitant

  (comparing AUC & Cmax of Days 1&3 of the Period One and Two)

Secondary Outcomes (1)

• Safety evaluations of AEs and changes in laboratory values, ECGs, vitals evaluated during the study

  (Day -1 and Days 1-4 of the Period One and Two, at follow-up visit)

Study Arms (3)

Subjects in Part A

EXPERIMENTAL

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.

Drug: casopitant; Drug: dolasetron

Subjects in Part B

EXPERIMENTAL

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.

Drug: casopitant; Drug: granisetron

Subjects in Part C

EXPERIMENTAL

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.

Drug: casopitant; Drug: rosiglitazone

Interventions

casopitant 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.

Subjects in Part A; Subjects in Part B; Subjects in Part C

dolasetron 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 A

granisetron 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 B

rosiglitazone 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.

Subjects in Part C

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Evansville, Indiana, 47714, United States

Location

Related Publications (1)

• 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.

  PMID: 19205754 RESULT

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
• Results for study NKV110483 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Nausea; Vomiting

Interventions

casopitant; dolasetron; Granisetron; Rosiglitazone

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiazolidinediones; Thiazoles; Sulfur Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: August 2, 2007
• First Posted: August 6, 2007
• Study Start: July 23, 2007
• Primary Completion: September 21, 2007
• Study Completion: September 21, 2007
• Last Updated: August 3, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share

Locations

US (1)