Pharmacokinetic Study Comparing Blood Levels of Dasatinib in Healthy Participants Who Received the Tablet Formulation With Those Who Received Liquid and Tablet-dispersed Formulations

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 1

Conditions: Pharmacokinetic Study in Healthy Participants

Treatments: Drug: Dasatinib as dispersed tablets; Drug: Dasatinib as tablets; Drug: Dasatinib as liquid

Study type: Interventional

Funder types: Industry

Identifiers

NCT01392703

CA180-352

Details and patient eligibility

About

The purpose of the study is to compare the blood levels of dasatinib in healthy participants who received tablet formulation with those of healthy participants who received liquid and tablet-dispersed formulations of the drug.

Enrollment: 141 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Healthy participants, defined as having no clinically relevant deviation from normal in medical history, physical examination, electrocardiogram (ECG) findings, and clinical laboratory tests findings.
• Body mass index of 18 to 32 kg/m^2, inclusive
• Age from 18 to 55 years
• Men and women who were not of childbearing potential (ie, who were postmenopausal or surgically sterile)
• All women must have had a negative serum or urine pregnancy test result(minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) at screening and within 24 hours prior to dosing with study drug
• Women must not have been breastfeeding
• Sexually active fertile men with female partners of childbearing potential were required to abide by the requirement to use effective birth control for the entire study and for 90 days after the date of last treatment
• Men must have agreed not to donate sperm for the entire study and for 90 days after the day of last study treatment
• Participants must have agreed not to make blood donations, including red blood cells, plasma, platelets, or whole blood, for the entire study and for 8 weeks after the day of last study treatment

Key Exclusion Criteria:

• Any significant acute or chronic medical illness

• Current or recent (within 3 months of study drug administration) disease of the gastrointestinal (GI) tract that may impact drug absorption and may affect pharmacokinetics of the study drugs or any GI tract surgery that may impact drug absorption

• Any major surgery, as determined by the investigator, within 4 weeks of dosing in Period 1

• Blood transfusion within 4 weeks of study drug administration

• Donation of >400 mL of blood within 8 weeks prior to study dosing or donation of plasma within 4 weeks prior to study dosing

• Inability to tolerate oral medication

• Inability to tolerate orange juice

• Inability to undergo venipuncture and/or tolerate venous access

• Use of tobacco or nicotine-containing products within 6 months prior to check-in, or positive nicotine test at screening and/or check-in

• Consumption of more than 3 cups of coffee or other caffeine-containing products a day, or 5 cups of tea a day

• Recent (within 6 months of study drug administration) drug or alcohol abuse

• Positive blood screen for hepatitis C antibody; hepatitis B surface antigen; and HIV-1, HIV-2, or HIV antibody

• History of any significant drug allergy or asthma

• Evidence of organ dysfunction or any clinically relevant deviation from normal in physical examination, ECG findings, vital signs, or clinical laboratory test findings.

• Any of the following on 12-lead ECG prior to study drug administration, confirmed by repeat ECG:

  • PR ≥210 ms
  • QRS ≥120 ms
  • QT ≥500 ms
  • QTcF ≥450 ms

Trial design

141 participants in 3 patient groups

Dasatinib, 100 mg as tablets + water

Other group

Description:

Treatment A. Participants were randomized to and received treatment in 1 of 6 sequences (ABC, ACB, BCA, BAC, CAB, or CBA), administered over 3 1-day treatment periods (Days 1, 5, and 9), with treatment changing to next in the sequence at start of each new period. A 3-day washout period followed treatment periods 1 and 2.

Treatment:

Drug: Dasatinib as tablets

Dasatinib, 100 mg as liquid + water

Other group

Description:

Treatment B. Participants were randomized to and received treatment in 1 of 6 sequences (ABC, ACB, BCA, BAC, CAB, or CBA), administered over 3 1-day treatment periods (Days 1, 5, and 9), with treatment changing to next in the sequence at start of each new period. A 3-day washout period followed treatment periods 1 and 2.

Treatment:

Drug: Dasatinib as liquid

Dasatinib, 100 mg as tablets in orange juice + water

Other group

Description:

Treatment C. Participants were randomized to and received treatment in 1 of 6 sequences (ABC, ACB, BCA, BAC, CAB, or CBA), administered over 3 1-day treatment periods (Days 1, 5, and 9), with treatment changing to next in the sequence at start of each new period. A 3-day washout period followed treatment periods 1 and 2.

Treatment:

Drug: Dasatinib as dispersed tablets