Effects of Gastric pH on the Pharmacokinetics of Dasatinib

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Leslie Benet, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01398046
First received: July 5, 2011
Last updated: October 15, 2013
Last verified: October 2013

July 5, 2011
October 15, 2013
August 2011
February 2014   (final data collection date for primary outcome measure)
  • Area-Under-the Concentration Curve from zero-to-twenty two hours (AUC,0-22) of Dasatinib [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
    The primary outcome measure will be dasatinib area-under-the-concentration curve (AUC) values from zero-to-twenty two (0-22) hours. Values from Experiemntal Arms of the study (Dasatinib plus Rabeprazole; Dasatinib plus Rabeprazole AND Betaine Hydrochloride) will be compared against the active comparator (dasatinib alone) and tested for statistical significance.
  • Area-Under-the Concentration Curve from zero-to-infinity (AUC,0-inf) of Dasatinib [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
    The primary outcome measure will be dasatinib area-under-the-concentration curve (AUC) values from zero-to-infinite time (0-inf). Values from Experiemntal Arms of the study (Dasatinib plus Rabeprazole; Dasatinib plus Rabeprazole AND Betaine Hydrochloride) will be compared against the active comparator (dasatinib alone) and tested for statistical significance.
Pharmacokinetics of dasatinib [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
The primary outcome measure will be dasatinib area-under-the-concentration curve (AUC) values from zero-to-twenty four (0-24) hours and zero-to-infinity (0-INF). Values from Experiemntal Arms of the study (Dasatinib plus Rabeprazole; Dasatinib plus Rabeprazole AND Betaine Hydrochloride) will be compared against the active comparator (dasatinib alone) and tested for statistical significance.
Complete list of historical versions of study NCT01398046 on ClinicalTrials.gov Archive Site
Maximum Concentration of Dasatinib [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
The maximum plasma concentration (Cmax) will also be measured. Values from Experiemntal Arms of the study (Dasatinib plus Rabeprazole; Dasatinib plus Rabeprazole AND Betaine Hydrochloride) will be compared against the active comparator (Dasatinib alone) and tested for statistical significance.
Same as current
Not Provided
Not Provided
 
Effects of Gastric pH on the Pharmacokinetics of Dasatinib
Effects of Gastric pH on the Pharmacokinetics of Dasatinib in Healthy Volunteers

The goal of this study is to evaluate the ability of a natural supplement (betaine hydrochloride) to affect the absorption of dasatinib in healthy volunteers. The investigators predict that betaine hydrochloride will increase the absorption of dasatinib, in volunteers pre-treated with proton-pump inhibitors (PPIs).

Not Provided
Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Healthy
  • Drug: Dasatinib
    dasatinib (100mg) PO x1
  • Drug: Dasatinib plus Rabeprazole
    Rabeprazole (20mg) PO twice daily (Days 1-3); Dasatinib (100mg) PO x1 (Day 4)
  • Drug: Dasatinib plus Rabeprazole AND Betaine Hydrochloride
    Rabeprazole (20mg) PO twice daily (Days 1-3); Betaine Hydrochloride (1500mg) PO x1 AND Dasatinib (100mg) PO x1 on Day 4
  • Active Comparator: Dasatinib
    Intervention: Drug: Dasatinib
  • Experimental: Dasatinib plus Rabeprazole
    Intervention: Drug: Dasatinib plus Rabeprazole
  • Experimental: Dasatinib plus Rabeprazole AND Betaine Hydrochloride
    Intervention: Drug: Dasatinib plus Rabeprazole AND Betaine Hydrochloride
Yago MR, Frymoyer AR, Smelick GS, Frassetto LA, Budha NR, Dresser MJ, Ware JA, Benet LZ. Gastric reacidification with betaine HCl in healthy volunteers with rabeprazole-induced hypochlorhydria. Mol Pharm. 2013 Nov 4;10(11):4032-7. doi: 10.1021/mp4003738. Epub 2013 Sep 10.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
18
February 2014
February 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male or female 18-59 years of age
  • Healthy adult with no active medical problems or significant chronic diseases as determined by the study doctor based on history, physical exam and laboratory evaluations
  • BMI between 18.5-30 kg/m2
  • Taking no medications 2 weeks before and during the study enrollment, including drugs of abuse, prescription or over-the-counter (OTC) medications (except acetaminophen)
  • Subjects able to maintain adequate birth control during the study independent of hormonal contraceptive use
  • Be able to provide written informed consent and comply with requirements of the study
  • Avoid eating grapefruit and drinking grapefruit juice from 7 days before the first study day until the completion of the entire study
  • Abstinence from alcoholic beverages, caffeinated beverages and orange juice from 3pm the night before a study day until completion of that study day
  • Fast from food and beverages at least 8 hours prior to medication dosing
  • Be able to read, speak, and understand English

Exclusion Criteria:

  • Subjects with a history of gastrointestinal disease including gastroesophageal reflux disease, gastritis, peptic ulcer disease, or dyspepsia
  • Subjects with a fasting gastric pH of > 4 (i.e. hypochlorhydria)
  • Subjects with a history of dysphagia, achalasia, or difficulty swallowing capsules, tablets, or pills
  • Subjects on prescription or chronic over-the-counter (OTC) medications (including hormonal contraceptives)
  • Subjects with known allergies to rabeprazole or any other proton pump inhibitors (PPI's) or betaine hydrochloride
  • Subjects who smoke tobacco
  • Subjects with ongoing alcohol or illegal drug use
  • Subjects who are pregnant, lactating, or attempting to conceive
  • Subjects unable to maintain adequate birth control during the study
Both
18 Years to 59 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01398046
Dasatinib-63-03
Yes
Leslie Benet, University of California, San Francisco
University of California, San Francisco
Genentech
Principal Investigator: Leslie Z Benet, Ph.D University of California, San Francisco
Principal Investigator: Lynda Frassetto, M.D. University of California, San Francisco
University of California, San Francisco
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP