Trial Outcomes & Findings for A Drug Interaction Study of Tasisulam in Patients With Advanced Cancer or Lymphoma (NCT NCT01185548)
NCT ID: NCT01185548
Last Updated: 2018-10-19
Results Overview
AUC0-∞ is defined as the area under the concentration time curve from time 0 to infinity.
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
4 participants
Primary outcome timeframe
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
Results posted on
2018-10-19
Participant Flow
Participant milestones
| Measure |
All Participants
Period 1: 500 milligram (mg) tolbutamide administered once on Day 1
Period 2: 500 mg of tolbutamide and individualized tasisulam dose (based on AUCalb) administered once on Day 1
Period 3: individualized tasisulam dose (based on AUCalb) administered once on Day 1 and 500 mg tolbutamide administered once on day 4
|
|---|---|
|
Period 1 : Tolbutamide
STARTED
|
4
|
|
Period 1 : Tolbutamide
COMPLETED
|
4
|
|
Period 1 : Tolbutamide
NOT COMPLETED
|
0
|
|
Period 2: Tasisulam and Tolbutamide
STARTED
|
4
|
|
Period 2: Tasisulam and Tolbutamide
COMPLETED
|
2
|
|
Period 2: Tasisulam and Tolbutamide
NOT COMPLETED
|
2
|
|
Period 3: Tasisulam and Tolbutamide
STARTED
|
2
|
|
Period 3: Tasisulam and Tolbutamide
COMPLETED
|
2
|
|
Period 3: Tasisulam and Tolbutamide
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
All Participants
Period 1: 500 milligram (mg) tolbutamide administered once on Day 1
Period 2: 500 mg of tolbutamide and individualized tasisulam dose (based on AUCalb) administered once on Day 1
Period 3: individualized tasisulam dose (based on AUCalb) administered once on Day 1 and 500 mg tolbutamide administered once on day 4
|
|---|---|
|
Period 2: Tasisulam and Tolbutamide
Sponsor Decision
|
2
|
Baseline Characteristics
A Drug Interaction Study of Tasisulam in Patients With Advanced Cancer or Lymphoma
Baseline characteristics by cohort
| Measure |
All Participants
n=4 Participants
Three study periods: Period 1 which was tolbutamide only and lasted 4 days and Periods 2 and 3 which had continued access to tasisulam every 28 days until disease progression:
Period 1: 500 mg tolbutamide administered once on Day 1.
Period 2: 500 mg of tolbutamide and individualized tasisulam dose administered once on Day 1.
Period 3: individualized tasisulam dose administered once on Day 1 and 500 mg tolbutamide administered once on Day 4.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
2 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 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
|
4 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
United Kingdom
|
4 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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 dosePopulation: All enrolled participants who started Period 2 (tasisulam and tolbutamide).
AUC0-∞ is defined as the area under the concentration time curve from time 0 to infinity.
Outcome measures
| Measure |
Period 2: Tasisulam and Tolbutamide
n=4 Participants
Period 2: 500 mg of tolbutamide and individualized tasisulam dose (based on AUCalb) administered once on Day 1
|
Tasisulam and Tolbutamide: Period 2
Period 2: 500 mg of tolbutamide and individualized tasisulam dose (based on AUCalb) administered once on Day 1.
|
Tasisulam and Tolbutamide: Period 3
Period 3: individualized tasisulam dose (based on AUCalb) administered once on Day 1 and 500 mg tolbutamide administered once on Day 4.
|
|---|---|---|---|
|
Pharmacokinetics of Tolbutamide, Concurrent Dosing, Area Under the Curve (AUC 0-∞)
|
2670000 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 20
|
—
|
—
|
SECONDARY outcome
Timeframe: Period 3 Predose; and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 24, 48, 96, and 264 hours post tolbutamide dosePopulation: All enrolled participants who started period 3 (tasisulam then tolbutamide).
AUC0-∞ is defined as the area under the concentration time curve from time 0 to infinity.
Outcome measures
| Measure |
Period 2: Tasisulam and Tolbutamide
n=2 Participants
Period 2: 500 mg of tolbutamide and individualized tasisulam dose (based on AUCalb) administered once on Day 1
|
Tasisulam and Tolbutamide: Period 2
Period 2: 500 mg of tolbutamide and individualized tasisulam dose (based on AUCalb) administered once on Day 1.
|
Tasisulam and Tolbutamide: Period 3
Period 3: individualized tasisulam dose (based on AUCalb) administered once on Day 1 and 500 mg tolbutamide administered once on Day 4.
|
|---|---|---|---|
|
Pharmacokinetics of Tolbutamide, Staggered Dosing in Period 3, Area Under the Curve (AUC 0-∞)
|
2700000 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation NA • Interval 4.03 to 6.0
There were not a sufficient number of participants to calculate the geometric coefficient of variation.
|
—
|
—
|
SECONDARY outcome
Timeframe: 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 dosePopulation: All enrolled participants who started Periods 1, 2, or 3.
Outcome measures
| Measure |
Period 2: Tasisulam and Tolbutamide
n=4 Participants
Period 2: 500 mg of tolbutamide and individualized tasisulam dose (based on AUCalb) administered once on Day 1
|
Tasisulam and Tolbutamide: Period 2
n=4 Participants
Period 2: 500 mg of tolbutamide and individualized tasisulam dose (based on AUCalb) administered once on Day 1.
|
Tasisulam and Tolbutamide: Period 3
n=2 Participants
Period 3: individualized tasisulam dose (based on AUCalb) administered once on Day 1 and 500 mg tolbutamide administered once on Day 4.
|
|---|---|---|---|
|
Pharmacokinetics of Tolbutamide, Maximum Concentration (Cmax)
|
39600 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 26
|
39800 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 18
|
48000 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation NA
There were not a sufficient number of participants to calculate the geometric coefficient of variation.
|
SECONDARY outcome
Timeframe: 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 dosePopulation: All enrolled participants who started Periods 1, 2, or 3.
Outcome measures
| Measure |
Period 2: Tasisulam and Tolbutamide
n=4 Participants
Period 2: 500 mg of tolbutamide and individualized tasisulam dose (based on AUCalb) administered once on Day 1
|
Tasisulam and Tolbutamide: Period 2
n=4 Participants
Period 2: 500 mg of tolbutamide and individualized tasisulam dose (based on AUCalb) administered once on Day 1.
|
Tasisulam and Tolbutamide: Period 3
n=2 Participants
Period 3: individualized tasisulam dose (based on AUCalb) administered once on Day 1 and 500 mg tolbutamide administered once on Day 4.
|
|---|---|---|---|
|
Pharmacokinetics of Tolbutamide, Observed Time at Maximal Concentration (Tmax)
|
2.25 hours
Interval 2.0 to 3.0
|
5.00 hours
Interval 1.5 to 8.0
|
5.02 hours
Interval 4.03 to 6.0
|
Adverse Events
Tolbutamide
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Tasisulam and Tolbutamide
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Tasisulam
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Tolbutamide
n=4 participants at risk
Adverse events (AEs) that occurred during Period 1 and during Period 2 when 500 mg tolbutamide was administered orally prior to individualized intravenous dosing (based on AUCalb) of tasisulam.
|
Tasisulam and Tolbutamide
n=4 participants at risk
AEs that occurred during Periods 2 and 3 when both 500 mg oral tolbutamide and individualized intravenous tasisulam (based on AUCalb) were administered.
|
Tasisulam
n=2 participants at risk
AEs that occurred during Period 3 Day 1 through Day 4 until just before 500 mg oral tolbutamide was administered on Day 4, 72 hours.
|
|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
Other adverse events
| Measure |
Tolbutamide
n=4 participants at risk
Adverse events (AEs) that occurred during Period 1 and during Period 2 when 500 mg tolbutamide was administered orally prior to individualized intravenous dosing (based on AUCalb) of tasisulam.
|
Tasisulam and Tolbutamide
n=4 participants at risk
AEs that occurred during Periods 2 and 3 when both 500 mg oral tolbutamide and individualized intravenous tasisulam (based on AUCalb) were administered.
|
Tasisulam
n=2 participants at risk
AEs that occurred during Period 3 Day 1 through Day 4 until just before 500 mg oral tolbutamide was administered on Day 4, 72 hours.
|
|---|---|---|---|
|
General disorders
Chest pain
|
0.00%
0/4
|
0.00%
0/4
|
50.0%
1/2 • Number of events 1
|
|
General disorders
Fatigue
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
|
General disorders
Mucosal inflammation
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
|
Hepatobiliary disorders
Hepatic pain
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/2
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
|
Infections and infestations
Rhinitis
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/4
|
50.0%
2/4 • Number of events 2
|
50.0%
1/2 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/4
|
50.0%
2/4 • Number of events 2
|
0.00%
0/2
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
|
Gastrointestinal disorders
Vomiting
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/2
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/4
|
25.0%
1/4 • Number of events 2
|
0.00%
0/2
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/2
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
|
Nervous system disorders
Dizziness
|
0.00%
0/4
|
50.0%
2/4 • Number of events 4
|
0.00%
0/2
|
|
Nervous system disorders
Lethargy
|
0.00%
0/4
|
50.0%
2/4 • Number of events 2
|
0.00%
0/2
|
|
Nervous system disorders
Neuropathy peripheral
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
|
Nervous system disorders
Presyncope
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
|
Skin and subcutaneous tissue disorders
Jessner's lymphocytic infiltration
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/2
|
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