Clinical trial NCT01398046: Effects of Gastric pH on the Pharmacokinetics of Dasatinib
Official title: Effects of Gastric pH on the Pharmacokinetics of Dasatinib in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: dasatinib
betaine
betaine hydrochloride
pharmacokinetics
healthy volunteer
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2011-07-20
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Area-Under-the Concentration Curve from zero-to-twenty two hours (AUC,0-22) of Dasatinib
timeFrame: Day 4
measure: Area-Under-the Concentration Curve from zero-to-infinity (AUC,0-inf) of Dasatinib
timeFrame: Day 4
Secondary outcomes:
measure: Maximum Concentration of Dasatinib
timeFrame: Day 4
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Clinical Research Center, UCSF
state: California
Study officials:
affiliation: University of California, San Francisco
name: Leslie Z Benet, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Lynda Frassetto, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.