- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00896207
Studying Different Formulations of SR13668 in Healthy Volunteers
Single-Dose Phase 0 Exploratory Pharmacokinetic Clinical Trial Comparing Five Oral Formulations of SR13668, an Orally Active AKT Pathway Inhibitor
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Minnesota
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
Given orally as a single dose
Other Names:
|
Experimental: 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.
|
Given orally as a single dose
Other Names:
|
Experimental: Arm III
Participants receive a single dose of oral Akt inhibitor SR13668 in a Solutol® self-emulsifying solid dispersion capsule formulation.
|
Given orally as a single dose
Other Names:
|
Experimental: Arm IV
Participants receive a single dose of oral Akt inhibitor SR13668 in a Solutol®/vitamin E TGPS self-emulsifying solid dispersion capsule formulation.
|
Given orally as a single dose
Other Names:
|
Experimental: Arm V
Participants receive a single dose of oral Akt inhibitor SR13668 in a vitamin E TGPS self-emulsifying solid dispersion capsule formulation.
|
Given orally as a single dose
Other Names:
|
Experimental: Arm VI
Participants receive a single dose of oral Akt inhibitor SR13668 in a Myrj 53 self-emulsifying solid dispersion capsule formulation.
|
Given orally as a single dose
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Food effect on the bioavailability of SR13668 after oral administration
Time Frame: Up to 30 days after completion of study treatment
|
The first stage will be used to compare fed vs. fasted diet effect on the pharmacokinetics parameters under formulation 1.
|
Up to 30 days after completion of study treatment
|
Formulation effect on the bioavailability of SR13668 after oral administration
Time Frame: Up to 30 days after completion of study treatment
|
The second stage will be used to determine the formulation effects on the pharmacokinetics parameters, all under either fed or fasted diet as determined by the first stage.
|
Up to 30 days after completion of study treatment
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Solubility and stability of Akt inhibitor SR13668 in oral formulations selected for exploratory pharmacokinetics studies
Time Frame: Up to 30 days after completion of study treatment
|
Up to 30 days after completion of study treatment
|
Oral pharmacokinetics of a single low dose of Akt inhibitor SR13668
Time Frame: Up to 30 days after completion of study treatment
|
Up to 30 days after completion of study treatment
|
Metabolism of Akt inhibitor SR13668
Time Frame: Up to 30 days after completion of study treatment
|
Up to 30 days after completion of study treatment
|
Preliminary safety data for Akt inhibitor SR13668, graded according to NCI CTCAE version 3.0
Time Frame: Up to 30 days after completion of study treatment
|
Up to 30 days after completion of study treatment
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- NCI-2009-01106 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- P30CA015083 (U.S. NIH Grant/Contract)
- MAYO-MAY07-9-01 (Other Identifier: Mayo Clinic)
- CDR0000638390
- MAY-07-9-01
- MAY07-9-01 (Other Identifier: DCP)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Healthy, no Evidence of Disease
-
National Cancer Institute (NCI)CompletedHealthy, no Evidence of DiseaseUnited States
-
Cancer Research UKUnknownHealthy, no Evidence of DiseaseUnited Kingdom
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)CompletedHealthy, no Evidence of DiseaseUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedHealthy, No Evidence of DiseaseUnited States
-
National Cancer Institute (NCI)CompletedHealthy, no Evidence of DiseaseUnited States
-
National Cancer Institute (NCI)TerminatedHealthy, no Evidence of DiseaseUnited States
-
National Cancer Institute (NCI)CompletedHealthy, no Evidence of DiseaseUnited States
-
National Cancer Institute (NCI)Completed
-
National Cancer Institute (NCI)Completed
-
National Cancer Institute (NCI)Completed
Clinical Trials on Akt inhibitor SR13668
-
National Cancer Institute (NCI)CompletedRecurrent Squamous Cell Carcinoma of the Nasopharynx | Stage IV Squamous Cell Carcinoma of the NasopharynxUnited States, Singapore, China
-
National Cancer Institute (NCI)CompletedRecurrent Gastric Carcinoma | Adenocarcinoma of the Gastroesophageal Junction | Diffuse Gastric Adenocarcinoma | Gastric Intestinal Type Adenocarcinoma | Gastric Mixed AdenocarcinomaUnited States, Canada
-
PIQUR Therapeutics AGM.D. Anderson Cancer Center; Mayo Clinic; University College London Hospitals; Hospital... and other collaboratorsCompleted
-
National Cancer Institute (NCI)CompletedExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue | Nodal Marginal Zone B-cell Lymphoma | Recurrent Adult Diffuse Large Cell Lymphoma | Recurrent Adult Diffuse Mixed Cell Lymphoma | Recurrent Adult Diffuse Small Cleaved Cell Lymphoma | Recurrent Adult Immunoblastic... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Salivary Gland Carcinoma | Stage IVA Major Salivary Gland Cancer AJCC v7 | Stage IVB Major Salivary Gland Cancer AJCC v7 | Stage IVC Major Salivary Gland Cancer AJCC v7 | Salivary Gland Adenoid Cystic Carcinoma | Recurrent Oral Cavity Adenoid Cystic Carcinoma | Stage IVA Oral Cavity... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedStage IV Breast Cancer | Recurrent Breast Carcinoma | Stage IIIB Breast Cancer | Stage IIIC Breast CancerUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Uterine Corpus Carcinoma | Endometrial Clear Cell Adenocarcinoma | Endometrial Serous Adenocarcinoma | Endometrial Adenocarcinoma | Endometrial Adenosquamous CarcinomaUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Adult Acute Myeloid Leukemia | Adult Acute Megakaryoblastic Leukemia (M7) | Adult Acute Minimally Differentiated Myeloid Leukemia (M0) | Adult Acute Monoblastic Leukemia (M5a) | Adult Acute Monocytic Leukemia (M5b) | Adult Acute Myeloblastic Leukemia With Maturation (M2) | Adult Acute... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Ovarian SarcomaUnited States
-
National Cancer Institute (NCI)CompletedAdvanced Adult Hepatocellular Carcinoma | Localized Non-Resectable Adult Liver Carcinoma | Recurrent Adult Liver Carcinoma | Recurrent Gallbladder Carcinoma | Stage IV Distal Bile Duct Cancer | Stage IV Gallbladder Cancer | Unresectable Extrahepatic Bile Duct Carcinoma | Unresectable Gallbladder...United States