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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

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.

Condition or disease Intervention/treatment Phase
Lymphoma Advanced Cancer Drug: Tolbutamide Drug: Tasisulam Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : July 2010
Actual Primary Completion Date : December 2010
Actual Study Completion Date : December 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Tolbutamide

Arm Intervention/treatment
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.

Drug: Tolbutamide
Administered orally

Drug: Tasisulam
Administered intravenously
Other Name: LY573636




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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 ]
  3. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01185548


Locations
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United Kingdom
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Cardiff, South Glamorgan, United Kingdom, CF14 2TL
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Sheffield, Trent, United Kingdom, S10 2SJ
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Leeds, West Yorkshire, United Kingdom, LS9 7TF
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Leicester, United Kingdom, LE1 5WW
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
London, United Kingdom, WC1E 6BT
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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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

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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01185548    
Other Study ID Numbers: 13076
H8K-MC-JZAR ( Other Identifier: Eli Lilly and Company )
First Posted: August 20, 2010    Key Record Dates
Results First Posted: October 19, 2018
Last Update Posted: October 19, 2018
Last Verified: March 2018
Keywords provided by Eli Lilly and Company:
Advanced or Metastatic Solid Tumors or Lymphoma
Additional relevant MeSH terms:
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Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Tolbutamide
Hypoglycemic Agents
Physiological Effects of Drugs