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A Drug Interaction Study of Tasisulam in Patients With Advanced Cancer or Lymphoma (JZAR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01185548
Recruitment Status : Terminated (Terminated based on safety results from another trial)
First Posted : August 20, 2010
Results First Posted : October 19, 2018
Last Update Posted : October 19, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE August 18, 2010
First Posted Date  ICMJE August 20, 2010
Results First Submitted Date  ICMJE March 17, 2018
Results First Posted Date  ICMJE October 19, 2018
Last Update Posted Date October 19, 2018
Study Start Date  ICMJE July 2010
Actual Primary Completion Date December 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 17, 2018)
Pharmacokinetics of Tolbutamide, Concurrent Dosing, Area Under the Curve (AUC 0-∞) [ Time Frame: Period 2 Predose; and 0.5, 1, 1.5, 2, 2.5, 3, 4, 4.5, 6, 8, 24, 48, 72, 120, 168, 336 hours post tolbutamide dose ]
AUC0-∞ is defined as the area under the concentration time curve from time 0 to infinity.
Original Primary Outcome Measures  ICMJE
 (submitted: August 18, 2010)
Pharmacokinetics of tolbutamide, concurrent dosing, area under the curve (AUC 0-infinity) [ Time Frame: Period 2 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 17, 2018)
  • Pharmacokinetics of Tolbutamide, Staggered Dosing in Period 3, Area Under the Curve (AUC 0-∞) [ Time Frame: Period 3 Predose; and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 24, 48, 96, and 264 hours post tolbutamide dose ]
    AUC0-∞ is defined as the area under the concentration time curve from time 0 to infinity.
  • Pharmacokinetics of Tolbutamide, Maximum Concentration (Cmax) [ Time Frame: Period 1, 2, and 3 Predose; and 0.5, 1, 1.5, 2, 2.5, 3, 4, 4.5, 6, 8, 24, 48, 72, 96, 120, 168, 264, 336 hours post tolbutamide dose ]
  • Pharmacokinetics of Tolbutamide, Observed Time at Maximal Concentration (Tmax) [ Time Frame: Period 1, 2, and 3 Predose; and 0.5, 1, 1.5, 2, 2.5, 3, 4, 4.5, 6, 8, 24, 48, 72, 96, 120, 168, 264, 336 hours post tolbutamide dose ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2010)
  • Pharmacokinetics of tolbutamide, staggered dosing, area under the curve (AUC 0-infinity). [ Time Frame: Period 3 ]
  • Pharmacokinetics of Tolbutamide, Maximum Concentration (Cmax) [ Time Frame: Period 1, 2 and 3 ]
  • Pharmacokinetics of Tolbutamide, Observed Time at Maximal Concentration (Tmax) [ Time Frame: Period 1, 2 and 3 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Drug Interaction Study of Tasisulam in Patients With Advanced Cancer or Lymphoma
Official Title  ICMJE The Effect of Tasisulam on the CYP2C9-Mediated Metabolism of Tolbutamide: A Pharmacokinetic Interaction Study in Cancer Patients With Advanced and/or Metastatic Solid Tumors or Lymphoma
Brief Summary The purpose of this study was to assess the effect of tasisulam as an inhibitor of CYP2C9, using tolbutamide as a probe substrate. This study was to have 3 treatment periods, and continued access in an extension period. Period 1 is 4 days in length. Periods 2 and 3 are each approximately 28 days in length. Due to the early termination of the trial, only 1 Period 3 participant enrolled in the extension period before study termination.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Lymphoma
  • Advanced Cancer
Intervention  ICMJE
  • Drug: Tolbutamide
    Administered orally
  • Drug: Tasisulam
    Administered intravenously
    Other Name: LY573636
Study Arms  ICMJE Experimental: Tasisulam and Tolbutamide

Three study periods and continued access to tasisulam every 28 days (except Period 1 which was tolbutamide only and lasted 4 days) until disease progression:

Period 1: 500 milligram (mg) tolbutamide administered on Day 1.

Period 2: 500 mg of tolbutamide and individualized tasisulam dose [based on area under the curve albumin-corrected threshold (AUCalb)]. The AUCalb is a surrogate marker for unbound tasisulam, and this dosing approach represents the maximum level of unbound tasisulam which may be achieved clinically, administered on Day 1.

Period 3: Individualized tasisulam dose (based on AUCalb) administered on Day 1 and 500 mg tolbutamide administered on Day 4.

Interventions:
  • Drug: Tolbutamide
  • Drug: Tasisulam
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: April 12, 2011)
4
Original Estimated Enrollment  ICMJE
 (submitted: August 18, 2010)
50
Actual Study Completion Date  ICMJE December 2010
Actual Primary Completion Date December 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Have histologically or cytologically confirmed solid malignancy or lymphoma that is advanced and/or metastatic disease which has not responded to standard therapy or for which no standard therapy exists.
  2. Have given written informed consent prior to any study-specific procedures.
  3. Have a performance status of less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) scale and an estimated life expectancy of greater than 12 weeks.
  4. Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy, or other investigational therapy for at least 30 days (45 days for mitomycin-C or nitrosoureas) prior to study enrollment and recovered from the acute effects of therapy. Limited field radiotherapy is permitted (in consultation with the investigator).
  5. Have adequate organ function.
  6. Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures.
  7. Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 6 months following the last dose of study drug.
  8. Females with child-bearing potential must have had a negative serum pregnancy test less than 7 days prior to the first dose of study drug.

Exclusion Criteria:

  1. Have received treatment within 30 days of the initial dose of study drug with an experimental agent for noncancer indications that has not received regulatory approval for any indication.
  2. Have known allergies to tasisulam or related compounds.
  3. Have serious preexisting medical conditions.
  4. Show evidence of significant active neuropsychiatric disease or central nervous system (CNS) disease (for example, Alzheimer's disease or Parkinson's disease). Patients with active brain metastasis are excluded.
  5. Have current acute or chronic leukemia.
  6. Females who are pregnant or lactating.
  7. Have known positive test results in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb).
  8. History of severe allergies or multiple adverse drug reactions.
  9. Are persons who have previously completed or withdrawn from this study or any other study investigating tasisulam.
  10. Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study.
  11. Serious concomitant systemic disorder, including diabetes or active infection, incompatible with the study.
  12. Clinically significant cardiac symptomology.
  13. Patients being treated with warfarin.
  14. Patients being treated with sulfonylureas
  15. Regularly use drugs of abuse and/or show positive findings on urinary drug screening that is not in accordance with known/acceptable concomitant medication.
  16. Patients who have received medications that are known inducers or inhibitors of CYP2C9 within 30 days prior to enrollment.
  17. Have donated or lost blood of more than 500 milliliter (mL) within the last month.
  18. Have an average weekly alcohol intake that exceeds 21 units per week (males up to age 65) and 14 units per week (males over 65 and females) (1 unit = 12 ounces (oz) or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits).
  19. Failure for any reason to satisfy the investigator for adequate fitness to participate in the study.
  20. Screening albumin levels less than 30 grams/Liter (g/L).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01185548
Other Study ID Numbers  ICMJE 13076
H8K-MC-JZAR ( Other Identifier: Eli Lilly and Company )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
PRS Account Eli Lilly and Company
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP