Trial Outcomes & Findings for A Tasisulam and Midazolam Drug Interaction Study in Cancer Patients (NCT NCT01209832)
NCT ID: NCT01209832
Last Updated: 2019-03-18
Results Overview
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
11 participants
Primary outcome timeframe
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.
Results posted on
2019-03-18
Participant Flow
Participant milestones
| Measure |
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.
|
|---|---|
|
Period 1
STARTED
|
11
|
|
Period 1
Received At Least 1 Dose of Study Drug
|
10
|
|
Period 1
COMPLETED
|
10
|
|
Period 1
NOT COMPLETED
|
1
|
|
Period 2
STARTED
|
10
|
|
Period 2
COMPLETED
|
9
|
|
Period 2
NOT COMPLETED
|
1
|
|
Maintenance Period 1 (M1)
STARTED
|
4
|
|
Maintenance Period 1 (M1)
COMPLETED
|
4
|
|
Maintenance Period 1 (M1)
NOT COMPLETED
|
0
|
|
Maintenance Period 2 (M1)
STARTED
|
3
|
|
Maintenance Period 2 (M1)
COMPLETED
|
3
|
|
Maintenance Period 2 (M1)
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|
|
Period 1
Sponsor Decision and was not dosed
|
1
|
|
Period 2
Sponsor Decision
|
1
|
Baseline Characteristics
A Tasisulam and Midazolam Drug Interaction Study in Cancer Patients
Baseline characteristics by cohort
| Measure |
Midazolam + Tasisulam
n=10 Participants
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.
|
|---|---|
|
Age, Continuous
|
57 years
STANDARD_DEVIATION 9.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
France
|
10 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.Population: 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.
Outcome measures
| Measure |
Midazolam
n=10 Participants
Period 1 (7 days): 1.2 milligrams (mg) midazolam orally on Day 1.
|
Midazolam + Tasisulam
n=9 Participants
Period 2 (28 days): Tasisulam was dosed 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 followed by 1.2 mg midazolam orally on Day 8.
|
|---|---|---|
|
Midazolam Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to the Last Time Point With Measurable Concentrations (AUC 0-tlast)
|
25.9 nanograms*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 35
|
22.5 nanograms*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 55
|
PRIMARY outcome
Timeframe: 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.Population: 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.
Outcome measures
| Measure |
Midazolam
n=10 Participants
Period 1 (7 days): 1.2 milligrams (mg) midazolam orally on Day 1.
|
Midazolam + Tasisulam
n=9 Participants
Period 2 (28 days): Tasisulam was dosed 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 followed by 1.2 mg midazolam orally on Day 8.
|
|---|---|---|
|
Midazolam Pharmacokinetics: Maximum Concentration (Cmax)
|
9.07 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 41
|
9.48 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 51
|
PRIMARY outcome
Timeframe: 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.Population: 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.
Outcome measures
| Measure |
Midazolam
n=9 Participants
Period 1 (7 days): 1.2 milligrams (mg) midazolam orally on Day 1.
|
Midazolam + Tasisulam
n=9 Participants
Period 2 (28 days): Tasisulam was dosed 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 followed by 1.2 mg midazolam orally on Day 8.
|
|---|---|---|
|
Midazolam Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC 0-infinity)
|
27.0 nanograms*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 36
|
22.8 nanograms*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 54
|
SECONDARY outcome
Timeframe: Baseline to Day 15 of Maintenance Period up to 3 monthsPopulation: All participants who received study drug.
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.
Outcome measures
| Measure |
Midazolam
n=10 Participants
Period 1 (7 days): 1.2 milligrams (mg) midazolam orally on Day 1.
|
Midazolam + Tasisulam
Period 2 (28 days): Tasisulam was dosed 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 followed by 1.2 mg midazolam orally on Day 8.
|
|---|---|---|
|
Number of Participants With Tumor Response
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: 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.Population: All participants who received tasisulam and had pharmacokinetics data.
Outcome measures
| Measure |
Midazolam
n=9 Participants
Period 1 (7 days): 1.2 milligrams (mg) midazolam orally on Day 1.
|
Midazolam + Tasisulam
Period 2 (28 days): Tasisulam was dosed 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 followed by 1.2 mg midazolam orally on Day 8.
|
|---|---|---|
|
Tasisulam Pharmacokinetics: Maximum Concentration (Cmax)
|
358 micrograms per milliliter (mcg/mL)
Geometric Coefficient of Variation 17
|
—
|
SECONDARY outcome
Timeframe: 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.Population: All participants who received tasisulam and had pharmacokinetics data.
Tasisulam is highly bound to albumin. AUCalb is a surrogate measure of exposure to unbound (free) tasisulam.
Outcome measures
| Measure |
Midazolam
n=9 Participants
Period 1 (7 days): 1.2 milligrams (mg) midazolam orally on Day 1.
|
Midazolam + Tasisulam
Period 2 (28 days): Tasisulam was dosed 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 followed by 1.2 mg midazolam orally on Day 8.
|
|---|---|---|
|
Tasisulam Pharmacokinetics: Area Under the Concentration-Time Curve Above the Albumin Corrected Threshold (AUCalb)
|
5840 hour*micrograms/milliliter (h*mcg/mL)
Geometric Coefficient of Variation 50
|
—
|
Adverse Events
Midazolam
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Tasisulam and Midazolam
Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths
Tasisulam (M1)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Tasisulam (M2)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Midazolam
n=10 participants at risk
Period 1 (7 days): 1.2 milligrams (mg) midazolam orally on Day 1.
|
Tasisulam and Midazolam
n=10 participants at risk
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.
|
Tasisulam (M1)
n=4 participants at risk
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.
|
Tasisulam (M2)
n=3 participants at risk
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.
|
|---|---|---|---|---|
|
Infections and infestations
Febrile infection
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
Other adverse events
| Measure |
Midazolam
n=10 participants at risk
Period 1 (7 days): 1.2 milligrams (mg) midazolam orally on Day 1.
|
Tasisulam and Midazolam
n=10 participants at risk
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.
|
Tasisulam (M1)
n=4 participants at risk
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.
|
Tasisulam (M2)
n=3 participants at risk
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.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/10
|
20.0%
2/10 • Number of events 3
|
0.00%
0/4
|
0.00%
0/3
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Blood and lymphatic system disorders
Thrombotic thrombocytopenic purpura
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Cardiac disorders
Palpitations
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Ear and labyrinth disorders
Deafness
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Eye disorders
Dry eye
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/10
|
0.00%
0/10
|
25.0%
1/4 • Number of events 1
|
0.00%
0/3
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Gastrointestinal disorders
Colonic obstruction
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/10
|
30.0%
3/10 • Number of events 3
|
0.00%
0/4
|
0.00%
0/3
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/10
|
20.0%
2/10 • Number of events 2
|
0.00%
0/4
|
0.00%
0/3
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Gastrointestinal disorders
Nausea
|
10.0%
1/10 • Number of events 1
|
0.00%
0/10
|
0.00%
0/4
|
0.00%
0/3
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Gastrointestinal disorders
Vomiting
|
20.0%
2/10 • Number of events 2
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
|
General disorders
Asthenia
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
General disorders
Chest pain
|
0.00%
0/10
|
20.0%
2/10 • Number of events 2
|
0.00%
0/4
|
0.00%
0/3
|
|
General disorders
Fatigue
|
0.00%
0/10
|
50.0%
5/10 • Number of events 5
|
25.0%
1/4 • Number of events 1
|
0.00%
0/3
|
|
General disorders
Pain
|
10.0%
1/10 • Number of events 1
|
0.00%
0/10
|
0.00%
0/4
|
0.00%
0/3
|
|
General disorders
Pyrexia
|
10.0%
1/10 • Number of events 1
|
20.0%
2/10 • Number of events 3
|
0.00%
0/4
|
0.00%
0/3
|
|
General disorders
Thirst
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Infections and infestations
Bronchitis
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
25.0%
1/4 • Number of events 1
|
0.00%
0/3
|
|
Investigations
Blood creatinine increased
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Investigations
Platelet count decreased
|
0.00%
0/10
|
20.0%
2/10 • Number of events 2
|
0.00%
0/4
|
0.00%
0/3
|
|
Investigations
Weight decreased
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
10.0%
1/10 • Number of events 1
|
0.00%
0/10
|
0.00%
0/4
|
0.00%
0/3
|
|
Nervous system disorders
Ataxia
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Nervous system disorders
Dizziness
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Nervous system disorders
Headache
|
0.00%
0/10
|
20.0%
2/10 • Number of events 2
|
0.00%
0/4
|
0.00%
0/3
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Nervous system disorders
Somnolence
|
10.0%
1/10 • Number of events 1
|
0.00%
0/10
|
0.00%
0/4
|
0.00%
0/3
|
|
Psychiatric disorders
Depression
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.0%
2/10 • Number of events 2
|
0.00%
0/10
|
0.00%
0/4
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/10
|
30.0%
3/10 • Number of events 3
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/10
|
0.00%
0/10
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
25.0%
1/4 • Number of events 1
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Dermatitis bullous
|
0.00%
0/10
|
0.00%
0/10
|
25.0%
1/4 • Number of events 1
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
|
Vascular disorders
Haematoma
|
10.0%
1/10 • Number of events 1
|
0.00%
0/10
|
0.00%
0/4
|
0.00%
0/3
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60