Trial Outcomes & Findings for A Bioavailability Study of LY2452473 and Tadalafil (NCT NCT01401543)
NCT ID: NCT01401543
Last Updated: 2019-06-14
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
Predose up to 96 hours postdose for each of the 4 treatment periods
Results posted on
2019-06-14
Participant Flow
Participant milestones
| Measure |
Sequence 1
First intervention: A 5-milligram (mg) LY2452473 capsule and 5-mg tadalafil tablet administered orally, once.
Second intervention: A single combination tablet LY900010 (containing 5 mg LY2452473 with a larger particle size #3, d90 = 40 microns, and 5 mg tadalafil) administered orally, once.
Third intervention: A single combination tablet LY900010 (containing 5 mg LY2452473 with a smaller particle size #1, d90 = 10 microns, and 5 mg tadalafil) administered orally, once.
Fourth intervention: A single combination tablet LY900010 (containing 5 mg LY2452473 with an intermediate particle size #2, d90 = 25 microns, and 5 mg tadalafil) administered orally, once.
There was a washout period of at least 7 days between each intervention. d90 is a measurement of the distribution of particle widths such that 90% of the particles have a diameter less than the specified value.
|
Sequence 2
First intervention: A single combination tablet LY900010 (containing 5 mg LY2452473 with a smaller particle size #1, d90 = 10 microns, and 5 mg tadalafil) administered orally, once.
Second intervention: A 5-mg LY2452473 capsule and 5-mg tadalafil tablet administered orally, once.
Third intervention: A single combination tablet LY900010 (containing 5 mg LY2452473 with an intermediate particle size #2, d90 = 25 microns, and 5 mg tadalafil) administered orally, once.
Fourth intervention: A single combination tablet LY900010 (containing 5 mg LY2452473 with a larger particle size #3, d90 = 40 microns, and 5 mg tadalafil) administered orally, once.
There was a washout period of at least 7 days between each intervention. d90 is a measurement of the distribution of particle widths such that 90% of the particles have a diameter less than the specified value.
|
Sequence 3
First intervention: A single combination tablet LY900010 (containing 5 mg LY2452473 with an intermediate particle size #2, d90 = 25 microns, and 5 mg tadalafil) administered orally, once.
Second intervention: A single combination tablet LY900010 (containing 5 mg LY2452473 with a smaller particle size #1, d90 = 10 microns, and 5 mg tadalafil) administered orally, once.
Third intervention: A single combination tablet LY900010 (containing 5 mg LY2452473 with a larger particle size #3, d90 =40 microns, and 5 mg tadalafil) administered orally, once.
Fourth intervention: A 5-mg LY2452473 capsule and 5-mg tadalafil tablet administered orally, once.
There was a washout period of at least 7 days between each intervention. d90 is a measurement of the distribution of particle widths such that 90% of the particles have a diameter less than the specified value.
|
Sequence 4
First intervention: A single combination tablet LY900010 (containing 5 mg LY2452473 with a larger particle size #3, d90 = 40 microns, and 5 mg tadalafil) administered orally, once.
Second intervention: A single combination tablet LY900010 (containing 5 mg LY2452473 with an intermediate particle size #2, d90 = 25 microns, and 5 mg tadalafil) administered orally, once.
Third intervention: A 5-mg LY2452473 capsule and 5-mg tadalafil tablet administered orally, once.
Fourth intervention: A single combination tablet LY900010 (5 mg LY2452473 with a smaller particle size #1, d90 = 10 microns, and 5 mg tadalafil) administered orally, once.
There was a washout period of at least 7 days between each intervention. d90 is a measurement of the distribution of particle widths such that 90% of the particles have a diameter less than the specified value.
|
|---|---|---|---|---|
|
First Intervention
STARTED
|
6
|
6
|
6
|
6
|
|
First Intervention
COMPLETED
|
6
|
6
|
6
|
6
|
|
First Intervention
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
First Washout Period of 1 Week
STARTED
|
6
|
6
|
6
|
6
|
|
First Washout Period of 1 Week
COMPLETED
|
6
|
6
|
6
|
6
|
|
First Washout Period of 1 Week
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Second Intervention
STARTED
|
6
|
6
|
6
|
6
|
|
Second Intervention
COMPLETED
|
6
|
6
|
6
|
6
|
|
Second Intervention
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Second Washout Period of 1 Week
STARTED
|
6
|
6
|
6
|
6
|
|
Second Washout Period of 1 Week
COMPLETED
|
6
|
6
|
6
|
6
|
|
Second Washout Period of 1 Week
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Third Intervention
STARTED
|
6
|
6
|
6
|
6
|
|
Third Intervention
COMPLETED
|
6
|
6
|
6
|
6
|
|
Third Intervention
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Third Washout Period of 1 Week
STARTED
|
6
|
6
|
6
|
6
|
|
Third Washout Period of 1 Week
COMPLETED
|
6
|
6
|
6
|
6
|
|
Third Washout Period of 1 Week
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Fourth Intervention
STARTED
|
6
|
6
|
6
|
6
|
|
Fourth Intervention
COMPLETED
|
6
|
6
|
6
|
6
|
|
Fourth Intervention
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Bioavailability Study of LY2452473 and Tadalafil
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=24 Participants
All randomized participants
|
|---|---|
|
Age, Continuous
|
39.6 years
STANDARD_DEVIATION 13.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
23 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
24 Participants
n=5 Participants
|
|
Race, Customized
Black or African American
|
4 Participants
n=5 Participants
|
|
Race, Customized
White
|
20 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose up to 96 hours postdose for each of the 4 treatment periodsPopulation: Entire study population: All randomized participants.
Outcome measures
| Measure |
5 mg LY2452473 and 5 mg Tadalafil
n=24 Participants
Participants who were administered a 5-milligram (mg) LY2452473 capsule and 5-mg tadalafil tablet during any study period.
|
LY900010 (Particle Size #1)
n=24 Participants
Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with a smaller particle size #1, d90 = 10 microns, and 5 mg tadalafil) during any study period.
|
LY900010 (Particle Size #2)
n=24 Participants
Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with an intermediate particle size #2, d90 = 25 microns, and 5 mg tadalafil) during any study period.
|
LY900010 (Particle Size #3)
n=24 Participants
Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with a larger particle size #3, d90 = 40 microns, and 5 mg tadalafil) during any study period.
|
|---|---|---|---|---|
|
Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2452473
|
514 nanograms*hours per milliliter (ng*h/mL)
Standard Deviation 152
|
495 nanograms*hours per milliliter (ng*h/mL)
Standard Deviation 159
|
453 nanograms*hours per milliliter (ng*h/mL)
Standard Deviation 123
|
463 nanograms*hours per milliliter (ng*h/mL)
Standard Deviation 140
|
PRIMARY outcome
Timeframe: Predose up to 96 hours postdose for each of the 4 treatment periodsPopulation: Entire study population: All randomized participants.
Outcome measures
| Measure |
5 mg LY2452473 and 5 mg Tadalafil
n=24 Participants
Participants who were administered a 5-milligram (mg) LY2452473 capsule and 5-mg tadalafil tablet during any study period.
|
LY900010 (Particle Size #1)
n=24 Participants
Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with a smaller particle size #1, d90 = 10 microns, and 5 mg tadalafil) during any study period.
|
LY900010 (Particle Size #2)
n=24 Participants
Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with an intermediate particle size #2, d90 = 25 microns, and 5 mg tadalafil) during any study period.
|
LY900010 (Particle Size #3)
n=24 Participants
Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with a larger particle size #3, d90 = 40 microns, and 5 mg tadalafil) during any study period.
|
|---|---|---|---|---|
|
Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2452473
|
32.5 nanograms per milliliter (ng/mL)
Standard Deviation 8.16
|
27.1 nanograms per milliliter (ng/mL)
Standard Deviation 6.62
|
25.6 nanograms per milliliter (ng/mL)
Standard Deviation 7.41
|
24.7 nanograms per milliliter (ng/mL)
Standard Deviation 5.66
|
SECONDARY outcome
Timeframe: Predose up to 96 hours postdose for each of the 4 treatment periodsPopulation: Entire study population: All randomized participants.
Outcome measures
| Measure |
5 mg LY2452473 and 5 mg Tadalafil
n=24 Participants
Participants who were administered a 5-milligram (mg) LY2452473 capsule and 5-mg tadalafil tablet during any study period.
|
LY900010 (Particle Size #1)
n=24 Participants
Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with a smaller particle size #1, d90 = 10 microns, and 5 mg tadalafil) during any study period.
|
LY900010 (Particle Size #2)
n=24 Participants
Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with an intermediate particle size #2, d90 = 25 microns, and 5 mg tadalafil) during any study period.
|
LY900010 (Particle Size #3)
n=24 Participants
Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with a larger particle size #3, d90 = 40 microns, and 5 mg tadalafil) during any study period.
|
|---|---|---|---|---|
|
Pharmacokinetics: AUC(0-∞) of Tadalafil
|
2410 nanograms*hours per milliliter (ng*h/mL)
Standard Deviation 893
|
2400 nanograms*hours per milliliter (ng*h/mL)
Standard Deviation 1070
|
2240 nanograms*hours per milliliter (ng*h/mL)
Standard Deviation 676
|
2290 nanograms*hours per milliliter (ng*h/mL)
Standard Deviation 825
|
SECONDARY outcome
Timeframe: Predose up to 96 hours postdose for each of the 4 treatment periodsPopulation: Entire study population: All randomized participants.
Outcome measures
| Measure |
5 mg LY2452473 and 5 mg Tadalafil
n=24 Participants
Participants who were administered a 5-milligram (mg) LY2452473 capsule and 5-mg tadalafil tablet during any study period.
|
LY900010 (Particle Size #1)
n=24 Participants
Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with a smaller particle size #1, d90 = 10 microns, and 5 mg tadalafil) during any study period.
|
LY900010 (Particle Size #2)
n=24 Participants
Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with an intermediate particle size #2, d90 = 25 microns, and 5 mg tadalafil) during any study period.
|
LY900010 (Particle Size #3)
n=24 Participants
Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with a larger particle size #3, d90 = 40 microns, and 5 mg tadalafil) during any study period.
|
|---|---|---|---|---|
|
Pharmacokinetics: Cmax of Tadalafil
|
102 nanograms per milliliter (ng/mL)
Standard Deviation 31.2
|
74.4 nanograms per milliliter (ng/mL)
Standard Deviation 28.0
|
72.4 nanograms per milliliter (ng/mL)
Standard Deviation 19.0
|
70.0 nanograms per milliliter (ng/mL)
Standard Deviation 17.5
|
Adverse Events
5 mg LY2452473 and 5 mg Tadalafil
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
LY900010 (Particle Size #1)
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
LY900010 (Particle Size #2)
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
LY900010 (Particle Size #3)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
5 mg LY2452473 and 5 mg Tadalafil
n=24 participants at risk
Participants who were administered a 5-mg LY2452473 capsule and 5-mg tadalafil tablet during any study period.
|
LY900010 (Particle Size #1)
n=24 participants at risk
Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with a smaller particle size #1, d90 = 10 microns, and 5 mg tadalafil) during any study period.
|
LY900010 (Particle Size #2)
n=24 participants at risk
Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with an intermediate particle size #2, d90 = 25 microns, and 5 mg tadalafil) during any study period.
|
LY900010 (Particle Size #3)
n=24 participants at risk
Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with a larger particle size #3, d90 = 40 microns, and 5 mg tadalafil) during any study period.
|
|---|---|---|---|---|
|
Eye disorders
Scleral hyperaemia
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
0.00%
0/24
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/24
|
0.00%
0/24
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
0.00%
0/24
|
0.00%
0/24
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/24
|
0.00%
0/24
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/24
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
|
General disorders
Fatigue
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
0.00%
0/24
|
|
General disorders
Feeling hot
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
0.00%
0/24
|
|
General disorders
Sensation of pressure
|
0.00%
0/24
|
0.00%
0/24
|
4.2%
1/24 • Number of events 2
|
0.00%
0/24
|
|
General disorders
Vessel puncture site haematoma
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
0.00%
0/24
|
|
General disorders
Vessel puncture site pain
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
0.00%
0/24
|
0.00%
0/24
|
|
General disorders
Vessel puncture site swelling
|
0.00%
0/24
|
4.2%
1/24 • Number of events 2
|
0.00%
0/24
|
0.00%
0/24
|
|
Metabolism and nutrition disorders
Decreased appetite
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
0.00%
0/24
|
0.00%
0/24
|
|
Nervous system disorders
Dizziness
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/24
|
0.00%
0/24
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
|
Nervous system disorders
Headache
|
4.2%
1/24 • Number of events 1
|
20.8%
5/24 • Number of events 5
|
8.3%
2/24 • Number of events 2
|
4.2%
1/24 • Number of events 1
|
|
Nervous system disorders
Somnolence
|
4.2%
1/24 • Number of events 1
|
4.2%
1/24 • Number of events 1
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
|
Reproductive system and breast disorders
Penis disorder
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
0.00%
0/24
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
0.00%
0/24
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/24
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
|
Skin and subcutaneous tissue disorders
Seborrhoeic dermatitis
|
0.00%
0/24
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/24
|
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