A Phase 1 interventional study of Tasisulam and Midazolam in Advanced Cancer, sponsored by Eli Lilly and Company. Terminated at 3 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-03-18.
Sponsored by Eli Lilly and Company · Phase 1, Interventional, and Basic science
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.
Eli Lilly and Company is the lead sponsor of 2,048 studies on the registry; 140 are open to participants now.
Of its 521 completed or terminated interventional studies of FDA-regulated products, 341 (65%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Drug: Tasisulam · Drug: Midazolam
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.
Also known as: LY573636
1.2 milligrams (mg), administered orally once prior to the initiation of tasisulam therapy and once on Day 8 after initiation of tasisulam therapy
Midazolam Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to the Last Time Point With Measurable Concentrations (AUC 0-tlast)
Time frame: 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)
Time frame: 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)
Time frame: 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.
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.
Time frame: Baseline to Day 15 of Maintenance Period up to 3 months
Tasisulam Pharmacokinetics: Maximum Concentration (Cmax)
Time frame: 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.
Time frame: 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.
| Milestone | Midazolam + Tasisulam |
|---|---|
| Started | 11 |
| Received at least 1 dose of study drug | 10 |
| Completed | 10 |
| Not completed | 1 |
| Withdrew: Sponsor decision and was not dosed | 1 |
| Milestone | Midazolam + Tasisulam |
|---|---|
| Started | 10 |
| Completed | 9 |
| Not completed | 1 |
| Withdrew: Sponsor decision | 1 |
| Milestone | Midazolam + Tasisulam |
|---|---|
| Started | 4 |
| Completed | 4 |
| Not completed | 0 |
| Milestone | Midazolam + Tasisulam |
|---|---|
| Started | 3 |
| Completed | 3 |
| Not completed | 0 |
| nanograms*hour per milliliter (ng*h/mL) | Midazolam | Midazolam + Tasisulam |
|---|---|---|
| Midazolam Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to the Last Time Point With Measurable Concentrations (AUC 0-tlast) | 25.9 ± 35 | 22.5 ± 55 |
| nanograms per milliliter (ng/mL) | Midazolam | Midazolam + Tasisulam |
|---|---|---|
| Midazolam Pharmacokinetics: Maximum Concentration (Cmax) | 9.07 ± 41 | 9.48 ± 51 |
| nanograms*hour per milliliter (ng*h/mL) | Midazolam | Midazolam + Tasisulam |
|---|---|---|
| Midazolam Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC 0-infinity) | 27.0 ± 36 | 22.8 ± 54 |
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.
| Participants | Midazolam + Tasisulam |
|---|---|
| Number of Participants With Tumor Response | 0 |
| micrograms per milliliter (mcg/mL) | Tasisulam |
|---|---|
| Tasisulam Pharmacokinetics: Maximum Concentration (Cmax) | 358 ± 17 |
Tasisulam is highly bound to albumin. AUCalb is a surrogate measure of exposure to unbound (free) tasisulam.
| hour*micrograms/milliliter (h*mcg/mL) | Tasisulam |
|---|---|
| Tasisulam Pharmacokinetics: Area Under the Concentration-Time Curve Above the Albumin Corrected Threshold (AUCalb) | 5840 ± 50 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Midazolam | — | 0/10 (0%) | 7/10 (70%) |
| Tasisulam and Midazolam | — | 1/10 (10%) | 9/10 (90%) |
| Tasisulam (M1) | — | 0/4 (0%) | 2/4 (50%) |
| Tasisulam (M2) | — | 0/3 (0%) | 2/3 (66.7%) |
| Event | Midazolam | Tasisulam and Midazolam | Tasisulam (M1) | Tasisulam (M2) |
|---|---|---|---|---|
| Febrile infectionInfections and infestations | 0/10 | 1/10 | 0/4 | 0/3 |
| Event | Midazolam | Tasisulam and Midazolam | Tasisulam (M1) | Tasisulam (M2) |
|---|---|---|---|---|
| FatigueGeneral disorders | 0/10 | 5/10 | 1/4 | 0/3 |
| VomitingGastrointestinal disorders | 2/10 | 1/10 | 0/4 | 1/3 |
| PharyngitisInfections and infestations | 0/10 | 1/10 | 0/4 | 1/3 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 0/10 | 3/10 | 0/4 | 1/3 |
| AlopeciaSkin and subcutaneous tissue disorders | 0/10 | 0/10 | 0/4 | 1/3 |
| ConstipationGastrointestinal disorders | 0/10 | 3/10 | 0/4 | 0/3 |
| Abdominal painGastrointestinal disorders | 0/10 | 0/10 | 1/4 | 0/3 |
| Aspartate aminotransferase increasedInvestigations | 0/10 | 1/10 | 1/4 | 0/3 |
| Dermatitis acneiformSkin and subcutaneous tissue disorders | 0/10 | 1/10 | 1/4 | 0/3 |
| Dermatitis bullousSkin and subcutaneous tissue disorders | 0/10 | 0/10 | 1/4 | 0/3 |
All participants who received at least one dose of the study drug.
| Age, Continuous(years) | Midazolam + Tasisulam |
|---|---|
| Mean | 57 ± 9.4 |
| Sex: Female, Male(Participants) | Midazolam + Tasisulam |
|---|---|
| Female | 5 |
| Male | 5 |
| Ethnicity (NIH/OMB)(Participants) | Midazolam + Tasisulam |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 10 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Midazolam + Tasisulam |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 10 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(Participants) | Midazolam + Tasisulam |
|---|---|
| France | 10 |
This study is terminated, as verified in Dec 2018. You cannot join it, but the record below documents what was studied.
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