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Single-Dose Phase 0 Exploratory Pharmacokinetic Clinical Trial Comparing Five Oral Formulations of SR13668, an Orally Active AKT Pathway Inhibitor


Phase 1
18 Years
62 Years
Not Enrolling
Both
Healthy, no Evidence of Disease

Thank you

Trial Information

Single-Dose Phase 0 Exploratory Pharmacokinetic Clinical Trial Comparing Five Oral Formulations of SR13668, an Orally Active AKT Pathway Inhibitor


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.


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Food effect on the bioavailability of SR13668 after oral administration

Outcome Description:

The first stage will be used to compare fed vs. fasted diet effect on the pharmacokinetics parameters under formulation 1.

Outcome Time Frame:

Up to 30 days after completion of study treatment

Safety Issue:

No

Principal Investigator

Paul Limburg

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-01106

NCT ID:

NCT00896207

Start Date:

June 2009

Completion Date:

Related Keywords:

  • Healthy, no Evidence of Disease

Name

Location

Mayo ClinicRochester, Minnesota  55905