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| ID | Type | Description | Link |
|---|---|---|---|
| H8K-MC-JZAP | Other Identifier | Eli Lilly and Company | |
| 2010-020090-16 | EudraCT Number |
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Terminated based on safety results from another trial
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The purpose of this study is to evaluate whether tasisulam acts as an inducer of CYP3A using midazolam as a sensitive and specific probe substrate of CYP3A.
The study will also assess the safety and tolerability of tasisulam and midazolam given in combination and document any antitumor activity with tasisulam.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Drug Interaction arm | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tasisulam | Drug | Patient specific dose, administered intravenously, on Day 1 of a 28-day cycle. Minimum of one (1) 28-day cycle. Patients may continue to receive tasisulam until disease progression or until discontinuation criteria are met. |
| Measure | Description | Time Frame |
|---|---|---|
| Midazolam Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to the Last Time Point With Measurable Concentrations (AUC 0-tlast) | Period 1 and 2: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 9, 11, 24, 48, and 72 hours post-dose. | |
| Midazolam Pharmacokinetics: Maximum Concentration (Cmax) | Period 1 and 2: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 9, 11, 24, 48, and 72 hours post-dose. | |
| Midazolam Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC 0-infinity) | Period 1 and 2: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 9, 11, 24, 48, and 72 hours post-dose. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Tumor Response | Number of participants with tumor response = number of participants with complete response (CR) + number of participants with partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 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. | Bordeaux | 33076 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Midazolam + Tasisulam | Period 1 (7 days): 1.2 milligrams (mg) midazolam orally on Day 1. Period 2 (28 days): Tasisulam intravenously to target area under the curve above the albumin corrected threshold (AUCalb) in the range of 1200 to 6400 hour*micrograms per milliliter (h*mcg/mL) on Day 1 and 1.2 mg midazolam orally on Day 8. Maintenance Period 1 and 2 (35 days): Tasisulam was dosed intravenously to target AUCalb in the range of 1200 to 6400 h*mcg/mL on Day 1. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
|
| |||||||||||||||||||||
| Period 2 |
| ||||||||||||||||||||||
| Maintenance Period 1 (M1) |
| ||||||||||||||||||||||
| Maintenance Period 2 (M1) |
|
All participants who received at least one dose of the study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Midazolam + Tasisulam | Period 1 (7 days): 1.2 milligrams (mg) midazolam orally on Day 1. Period 2 (28 days): Tasisulam intravenously to target area under the curve above the albumin corrected threshold (AUCalb) in the range of 1200 to 6400 hour*micrograms per milliliter (h*mcg/mL) on Day 1 and 1.2 mg midazolam orally on Day 8. Maintenance Period (35 days): Tasisulam was dosed intravenously to target AUCalb in the range of 1200 to 6400 h*mcg/mL on Day 1. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Midazolam Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to the Last Time Point With Measurable Concentrations (AUC 0-tlast) | All participants who received study drug and had sufficient pharmacokinetics data to calculate AUC0-tlast. Analysis used data according to the treatment the participants actually received. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms*hour per milliliter (ng*h/mL) | Period 1 and 2: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 9, 11, 24, 48, and 72 hours post-dose. |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Midazolam | Period 1 (7 days): 1.2 milligrams (mg) midazolam orally on Day 1. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile infection | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 13.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 |
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| ID | Term |
|---|---|
| D009362 | Neoplasm Metastasis |
| D008223 | Lymphoma |
| ID | Term |
|---|---|
| D009385 | Neoplastic Processes |
| D009369 | Neoplasms |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C534068 | N-((5-bromo-2-thienyl)sulfonyl)-2,4-dichlorobenzamide |
| D008874 | Midazolam |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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|
| Midazolam | Drug | 1.2 milligrams (mg), administered orally once prior to the initiation of tasisulam therapy and once on Day 8 after initiation of tasisulam therapy |
|
| Baseline to Day 15 of Maintenance Period up to 3 months |
| Tasisulam Pharmacokinetics: Maximum Concentration (Cmax) | Period 2: Predose, preinfusion start, 1, 1.75, 2 (post end of infusion), 2.5, 3, 4, 6, 8, 24, 48, 72, 120, 168, and 336 hours. |
| Tasisulam Pharmacokinetics: Area Under the Concentration-Time Curve Above the Albumin Corrected Threshold (AUCalb) | Tasisulam is highly bound to albumin. AUCalb is a surrogate measure of exposure to unbound (free) tasisulam. | Period 2: Predose, preinfusion start, 1, 1.75, 2 (post end of infusion), 2.5, 3, 4, 6, 8, 24, 48, 72, 120, 168, and 336 hours. |
| France |
| 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. | Lille | 59020 | France |
| 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. | Rennes | 35033 | France |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
|
|
| Primary | Midazolam Pharmacokinetics: Maximum Concentration (Cmax) | All participants who received study drug and had sufficient pharmacokinetics data to estimate Cmax. Analysis used data according to the treatment the participants actually received. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | Period 1 and 2: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 9, 11, 24, 48, and 72 hours post-dose. |
|
|
|
| Primary | Midazolam Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC 0-infinity) | All participants who received study drug and had sufficient pharmacokinetics data to calculate AUC0-infinity. Analysis used data according to the treatment the participants actually received. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms*hour per milliliter (ng*h/mL) | Period 1 and 2: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 9, 11, 24, 48, and 72 hours post-dose. |
|
|
|
| Secondary | Number of Participants With Tumor Response | Number of participants with tumor response = number of participants with complete response (CR) + number of participants with partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. | All participants who received study drug. | Posted | Count of Participants | Participants | No | Baseline to Day 15 of Maintenance Period up to 3 months |
|
|
|
| Secondary | Tasisulam Pharmacokinetics: Maximum Concentration (Cmax) | All participants who received tasisulam and had pharmacokinetics data. | Posted | Geometric Mean | Geometric Coefficient of Variation | micrograms per milliliter (mcg/mL) | Period 2: Predose, preinfusion start, 1, 1.75, 2 (post end of infusion), 2.5, 3, 4, 6, 8, 24, 48, 72, 120, 168, and 336 hours. |
|
|
|
| Secondary | Tasisulam Pharmacokinetics: Area Under the Concentration-Time Curve Above the Albumin Corrected Threshold (AUCalb) | Tasisulam is highly bound to albumin. AUCalb is a surrogate measure of exposure to unbound (free) tasisulam. | All participants who received tasisulam and had pharmacokinetics data. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*micrograms/milliliter (h*mcg/mL) | Period 2: Predose, preinfusion start, 1, 1.75, 2 (post end of infusion), 2.5, 3, 4, 6, 8, 24, 48, 72, 120, 168, and 336 hours. |
|
|
|
| 0 |
| 10 |
| 7 |
| 10 |
| EG001 | Tasisulam and Midazolam | Period 2 (28 days): Tasisulam intravenously to target area under the curve above the albumin corrected threshold (AUCalb) in the range of 1200 to 6400 hour*micrograms per milliliter (h*mcg/mL) on Day 1 and 1.2 mg midazolam orally on Day 8. | 1 | 10 | 9 | 10 |
| EG002 | Tasisulam (M1) | Maintenance Period 1 (35 days): Tasisulam was dosed intravenously to target AUCalb in the range of 1200 to 6400 h*mcg/mL on Day 1. | 0 | 4 | 2 | 4 |
| EG003 | Tasisulam (M2) | Maintenance Period 2 (35 days): Tasisulam was dosed intravenously to target AUCalb in the range of 1200 to 6400 h*mcg/mL on Day 1. | 0 | 3 | 2 | 3 |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Thrombotic thrombocytopenic purpura | Blood and lymphatic system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA 13.0 | Systematic Assessment |
|
| Deafness | Ear and labyrinth disorders | MedDRA 13.0 | Systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA 13.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Colitis | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Colonic obstruction | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Thirst | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 13.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 13.0 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 13.0 | Systematic Assessment |
|
| Blood lactate dehydrogenase increased | Investigations | MedDRA 13.0 | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA 13.0 | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA 13.0 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 13.0 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 13.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 13.0 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 13.0 | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 13.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Ataxia | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 13.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Dermatitis bullous | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA 13.0 | Systematic Assessment |
|
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| D009370 | Neoplasms by Histologic Type |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D006571 | Heterocyclic Compounds |