Studying Different Formulations of SR13668 in Healthy Volunteers

NCT ID: NCT00896207

Last Updated: 2014-10-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2010-03-31

Brief Summary

This randomized early phase I trial is studying different formulations of SR13668 in healthy volunteers. Giving SR13668 may help doctors learn more about how SR13668 is used by the body. It is not yet known which formulation of SR13668 is most effectively used by the body.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine which oral formulation of Akt inhibitor SR13668 provides the best bioavailability in normal, healthy volunteers.

SECONDARY OBJECTIVES:

I. Determine the oral pharmacokinetics of a single, low dose of Akt inhibitor SR13668 in healthy volunteers.

II. Characterize the metabolism of Akt inhibitor SR13668 in healthy volunteers. III. Collect preliminary safety data for Akt inhibitor SR13668 in healthy volunteers.

OUTLINE:

STAGE 1 (for the first 6 participants enrolled in the study [closed to accrual as of August, 2009]): Participants are randomized to 1 of 2 arms.

ARM I: Participants complete an overnight fast of ≥ 10 hours, eat a high-fat (approximately 50% of total caloric content of the meal) and high-calorie (approximately 800-1,000 calories), and then receive a single dose of oral SR13668 in a PEG400/Labrasol® liquid formulation with 8 ounces of water. Participants may not eat for ≥ 4 hours after study drug administration.

ARM II: Participants complete an overnight fast of ≥ 10 hours and then receive a single dose of oral SR13668 in a PEG400/Labrasol® liquid formulation with 8 ounces of water. Participants may not eat for ≥ 4 hours after study drug administration.

STAGE 2 (for the next 12 participants enrolled in the study): The preferred dietary condition (Arm I) identified in stage 1 is used. Participants are randomized to 1 of 4 arms.

ARM III: Participants receive a single dose of oral Akt inhibitor SR13668 in a Solutol® self-emulsifying solid dispersion capsule formulation.

ARM IV: Participants receive a single dose of oral Akt inhibitor SR13668 in a Solutol®/vitamin E TGPS self-emulsifying solid dispersion capsule formulation.

ARM V: Participants receive a single dose of oral Akt inhibitor SR13668 in a vitamin E TGPS self-emulsifying solid dispersion capsule formulation.

ARM VI: Participants receive a single dose of oral Akt inhibitor SR13668 in a Myrj 53 self-emulsifying solid dispersion capsule formulation.

Blood and urine samples are collected at baseline and periodically during the 24 hours after study drug administration for pharmacokinetic analysis by high performance liquid chromatography assay.

After completion of study treatment, participants are followed by telephone at 7-10 days and at 30 days.

Conditions

Healthy, no Evidence of Disease

Study Design

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

Study Groups

Arm I

Participants complete an overnight fast of ≥ 10 hours, eat a high-fat (approximately 50% of total caloric content of the meal) and high-calorie (approximately 800-1,000 calories) meal, and then receive a single dose of oral SR13668 in a PEG400/Labrasol® liquid formulation with 8 ounces of water. Participants may not eat for ≥ 4 hours after study drug administration.

Group Type: EXPERIMENTAL

Akt inhibitor SR13668

Intervention Type: DRUG

Given orally as a single dose

Arm II

Participants complete an overnight fast of ≥ 10 hours and then receive a single dose of oral SR13668 in a PEG400/Labrasol® liquid formulation with 8 ounces of water. Participants may not eat for ≥ 4 hours after study drug administration.

Group Type: EXPERIMENTAL

Akt inhibitor SR13668

Intervention Type: DRUG

Given orally as a single dose

Arm III

Participants receive a single dose of oral Akt inhibitor SR13668 in a Solutol® self-emulsifying solid dispersion capsule formulation.

Group Type: EXPERIMENTAL

Akt inhibitor SR13668

Intervention Type: DRUG

Given orally as a single dose

Arm IV

Participants receive a single dose of oral Akt inhibitor SR13668 in a Solutol®/vitamin E TGPS self-emulsifying solid dispersion capsule formulation.

Group Type: EXPERIMENTAL

Akt inhibitor SR13668

Intervention Type: DRUG

Given orally as a single dose

Arm V

Participants receive a single dose of oral Akt inhibitor SR13668 in a vitamin E TGPS self-emulsifying solid dispersion capsule formulation.

Group Type: EXPERIMENTAL

Akt inhibitor SR13668

Intervention Type: DRUG

Given orally as a single dose

Arm VI

Participants receive a single dose of oral Akt inhibitor SR13668 in a Myrj 53 self-emulsifying solid dispersion capsule formulation.

Group Type: EXPERIMENTAL

Akt inhibitor SR13668

Intervention Type: DRUG

Given orally as a single dose

Interventions

Akt inhibitor SR13668

Given orally as a single dose

Intervention Type: DRUG

Other Intervention Names

SRI13668

Eligibility Criteria

Inclusion Criteria

• Healthy volunteer
• ECOG performance status 0
• Leukocyte count ≥ 3,000/mm^3
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin normal
• Alkaline phosphatase ≤ 1.5 times upper limit of normal (ULN)
• ALT ≤ 1.5 times ULN
• Direct bilirubin ≤ 1.5 times ULN
• Sodium ≤ 1.5 times ULN
• Potassium ≤ 1.5 times ULN
• Creatinine ≤ 1.5 times ULN OR calculated creatinine clearance ≥ 30 mL/min
• Fasting blood glucose normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile participants must use effective barrier contraception
• Able and willing to fast overnight prior to study drug administration AND consume a high-fat meal on the day of study drug administration
• Willing to provide required blood and urine samples AND stay all day and overnight in the Clinical Research Unit
• Willing to abstain from alcoholic beverages and caffeine for ≥ 24 hours prior to study drug administration and until all blood and urine samples have been collected
• No cancer within the past 3 years except for nonmelanoma skin cancer, localized prostate cancer, superficial bladder cancer, or carcinoma in situ of the cervix
• No concurrent uncontrolled illness including, but not limited to, any of the following:

• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Severe chronic obstructive pulmonary disease requiring supplemental oxygen
• Hypertension that is difficult to control
• Psychiatric illness or social situation that would limit compliance with study requirements
• No diabetes mellitus
• No other condition that may, in the investigator's opinion, interfere with ingestion or absorption of oral medications (e.g., inflammatory bowel disease)
• No history of allergic-type reactions, including asthma and urticaria, or other intolerance to chemical compounds similar to the active study agent, indole-3-carbinol, or cruciferous vegetables (e.g., cabbage, cauliflower, broccoli, kale, and Brussels sprouts)
• More than 6 months since prior investigational agents
• More than 3 months since prior oral contraceptives (including Plan B method of contraception)

• No concurrent hormonal contraception
• More than 14 days since prior and no concurrent anticoagulant or antiplatelet medications
• More than 7 days since prior and no concurrent daily medications or nutritional supplements
• No prior gastrectomy that may, in the investigator's opinion, interfere with ingestion or absorption of oral medications
• No other concurrent medications

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 62 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul Limburg

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

NCI-2009-01106

Identifier Type: REGISTRY

Identifier Source: secondary_id

MAYO-MAY07-9-01

Identifier Type: -

Identifier Source: secondary_id

CDR0000638390

Identifier Type: -

Identifier Source: secondary_id

MAY-07-9-01

Identifier Type: -

Identifier Source: secondary_id

MAYO-MAY07-9-01

Identifier Type: OTHER

Identifier Source: secondary_id

MAY07-9-01

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-01106

Identifier Type: -

Identifier Source: org_study_id