Trial Outcomes & Findings for A Study to Evaluate the Effect of Genotype on LY2216684 (NCT NCT01460381)
NCT ID: NCT01460381
Last Updated: 2018-10-26
Results Overview
Blood samples were collected prior to and up to 120 hours following dosing of LY2216684 on Day 1 (Period 1) for the measurement of LY2216684 plasma concentrations.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
18 participants
Primary outcome timeframe
Predose up to 120 hours post administration of LY2216684
Results posted on
2018-10-26
Participant Flow
Participant milestones
| Measure |
LY2216684 + Quinidine (CYP2C19 Poor Metabolizers)
Participants were predicted to have a cytochrome P450 (CYP)2C19 poor metabolizer (PM) phenotype, as determined by genotyping analysis.
Period 1 (Days 1-7): a single, oral dose of 18 milligrams (mg) LY2216684 was administered on Day 1.
Period 2 (Days 8-15): 300 mg quinidine sulfate controlled release was administered orally, once daily on Days 8-15. Additionally, a single, oral dose of 18 mg LY2216684 was administered on Day 11.
|
LY2216684 (CYP2C19 Extensive Metabolizers)
Participants were predicted to have a cytochrome P450 (CYP)2C19 extensive metabolizer (EM) phenotype, as determined by genotyping analysis.
Period 1 (Days 1-7): a single, oral dose of 18 milligrams (mg) LY2216684 administered on Day 1.
Period 2 (Days 8-15): EM participants did not participate in this period.
|
|---|---|---|
|
Period 1 (Days 1-7)
STARTED
|
7
|
11
|
|
Period 1 (Days 1-7)
Received at Least 1 Dose of Study Drug
|
7
|
11
|
|
Period 1 (Days 1-7)
COMPLETED
|
7
|
11
|
|
Period 1 (Days 1-7)
NOT COMPLETED
|
0
|
0
|
|
Period 2 (Days 8-15)
STARTED
|
7
|
0
|
|
Period 2 (Days 8-15)
COMPLETED
|
6
|
0
|
|
Period 2 (Days 8-15)
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
LY2216684 + Quinidine (CYP2C19 Poor Metabolizers)
Participants were predicted to have a cytochrome P450 (CYP)2C19 poor metabolizer (PM) phenotype, as determined by genotyping analysis.
Period 1 (Days 1-7): a single, oral dose of 18 milligrams (mg) LY2216684 was administered on Day 1.
Period 2 (Days 8-15): 300 mg quinidine sulfate controlled release was administered orally, once daily on Days 8-15. Additionally, a single, oral dose of 18 mg LY2216684 was administered on Day 11.
|
LY2216684 (CYP2C19 Extensive Metabolizers)
Participants were predicted to have a cytochrome P450 (CYP)2C19 extensive metabolizer (EM) phenotype, as determined by genotyping analysis.
Period 1 (Days 1-7): a single, oral dose of 18 milligrams (mg) LY2216684 administered on Day 1.
Period 2 (Days 8-15): EM participants did not participate in this period.
|
|---|---|---|
|
Period 2 (Days 8-15)
Lost to Follow-up
|
1
|
0
|
Baseline Characteristics
A Study to Evaluate the Effect of Genotype on LY2216684
Baseline characteristics by cohort
| Measure |
LY2216684 + Quinidine (CYP2C19 Poor Metabolizers)
n=7 Participants
Participants were predicted to have a cytochrome P450 (CYP)2C19 poor metabolizer (PM) phenotype, as determined by genotyping analysis.
Period 1 (Days 1-7): a single, oral dose of 18 mg LY2216684 was administered on Day 1.
Period 2 (Days 8-15): 300 mg quinidine sulfate controlled release was administered orally, once daily on Days 8-15. Additionally, a single, oral dose of 18 mg LY2216684 was administered on Day 11.
|
LY2216684 (CYP2C19 Extensive Metabolizers)
n=11 Participants
Participants were predicted to have a cytochrome P450 (CYP)2C19 extensive metabolizer (EM) phenotype, as determined by genotyping analysis.
Period 1 (Days 1-7): a single, oral dose of 18 mg LY2216684 administered on Day 1.
Period 2 (Days 8-15): EM participants did not participate in this period.
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
40.1 years
STANDARD_DEVIATION 11.1 • n=5 Participants
|
44.9 years
STANDARD_DEVIATION 12.1 • n=7 Participants
|
43.1 years
STANDARD_DEVIATION 11.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
2 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
7 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose up to 120 hours post administration of LY2216684Population: Participants who received at least 1 dose of LY2216684 and had evaluable LY2216684 plasma concentration data were included in the analysis. Participants who vomited within twice the median time to maximum observed drug concentration (tmax) following dosing of LY2216684 were excluded from the analysis.
Blood samples were collected prior to and up to 120 hours following dosing of LY2216684 on Day 1 (Period 1) for the measurement of LY2216684 plasma concentrations.
Outcome measures
| Measure |
LY2216684 (CYP2C19 Poor Metabolizers)
n=7 Participants
Participants were predicted to have a cytochrome P450 (CYP)2C19 poor metabolizer (PM) phenotype, as determined by genotyping analysis.
Period 1 (Days 1-7): a single, oral dose of 18 mg LY2216684 was administered on Day 1.
|
LY2216684 (CYP2C19 Extensive Metabolizers)
n=7 Participants
Participants were predicted to have a cytochrome P450 (CYP)2C19 extensive metabolizer (EM) phenotype, as determined by genotyping analysis.
Period 1 (Days 1-7): a single, oral dose of 18 mg LY2216684 administered on Day 1.
|
|---|---|---|
|
Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity [AUC(0-∞)] of LY2216684 in Cytochrome P450 (CYP)2C19 Extensive Metabolizers (EM) Versus Poor Metabolizers (PM)
|
749 nanograms*hours per milliliter (ng*h/mL)
Geometric Coefficient of Variation 37
|
698 nanograms*hours per milliliter (ng*h/mL)
Geometric Coefficient of Variation 21
|
PRIMARY outcome
Timeframe: Predose up to 120 hours post administration of LY2216684Population: Participants who received at least 1 dose of LY2216684 and had evaluable LY2216684 plasma concentration data were included in the analysis. Participants who vomited within twice the median time to maximum observed drug concentration (tmax) following dosing of LY2216684 were excluded from the analysis.
Blood samples were collected prior to and up to 120 hours following dosing of LY2216684 on Day 1 (Period 1) for the measurement of LY2216684 plasma concentrations.
Outcome measures
| Measure |
LY2216684 (CYP2C19 Poor Metabolizers)
n=7 Participants
Participants were predicted to have a cytochrome P450 (CYP)2C19 poor metabolizer (PM) phenotype, as determined by genotyping analysis.
Period 1 (Days 1-7): a single, oral dose of 18 mg LY2216684 was administered on Day 1.
|
LY2216684 (CYP2C19 Extensive Metabolizers)
n=7 Participants
Participants were predicted to have a cytochrome P450 (CYP)2C19 extensive metabolizer (EM) phenotype, as determined by genotyping analysis.
Period 1 (Days 1-7): a single, oral dose of 18 mg LY2216684 administered on Day 1.
|
|---|---|---|
|
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2216684 in Cytochrome P450 (CYP)2C19 Extensive Metabolizers (EM) Versus Poor Metabolizers (PM)
|
54.7 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 28
|
54.8 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 25
|
PRIMARY outcome
Timeframe: Predose up to 120 hours post administration of LY2216684Population: Participants who received at least 1 dose of LY2216684 and had evaluable LY2216684 plasma concentration data were included in the analysis. Participants who vomited within twice the median time to maximum observed drug concentration (tmax) following dosing of LY2216684 were excluded from the analysis.
Blood samples were collected prior to and up to 120 hours following dosing of LY2216684 on Day 1 (Period 1) for the measurement of LY2216684 plasma concentrations.
Outcome measures
| Measure |
LY2216684 (CYP2C19 Poor Metabolizers)
n=7 Participants
Participants were predicted to have a cytochrome P450 (CYP)2C19 poor metabolizer (PM) phenotype, as determined by genotyping analysis.
Period 1 (Days 1-7): a single, oral dose of 18 mg LY2216684 was administered on Day 1.
|
LY2216684 (CYP2C19 Extensive Metabolizers)
n=7 Participants
Participants were predicted to have a cytochrome P450 (CYP)2C19 extensive metabolizer (EM) phenotype, as determined by genotyping analysis.
Period 1 (Days 1-7): a single, oral dose of 18 mg LY2216684 administered on Day 1.
|
|---|---|---|
|
Pharmacokinetics: Time to Maximum Observed Plasma Concentration (Tmax) of LY2216684 in Cytochrome P450 (CYP)2C19 Extensive Metabolizers (EM) Versus Poor Metabolizers (PM)
|
2.00 hours
Interval 1.0 to 3.02
|
2.00 hours
Interval 1.92 to 5.0
|
SECONDARY outcome
Timeframe: Predose up to 120 hours post administration of quinidinePopulation: Participants who received at least 1 dose of LY2216684 and had evaluable LY2216684 plasma concentration data were included in the analysis.
Blood samples were collected prior to and up to 120 hours following coadministration of LY2216684 and quinidine on Day 11 (Period 2) for the measurement of LY2216684 plasma concentrations.
Outcome measures
| Measure |
LY2216684 (CYP2C19 Poor Metabolizers)
n=7 Participants
Participants were predicted to have a cytochrome P450 (CYP)2C19 poor metabolizer (PM) phenotype, as determined by genotyping analysis.
Period 1 (Days 1-7): a single, oral dose of 18 mg LY2216684 was administered on Day 1.
|
LY2216684 (CYP2C19 Extensive Metabolizers)
Participants were predicted to have a cytochrome P450 (CYP)2C19 extensive metabolizer (EM) phenotype, as determined by genotyping analysis.
Period 1 (Days 1-7): a single, oral dose of 18 mg LY2216684 administered on Day 1.
|
|---|---|---|
|
Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity [(AUC(0-∞)] of LY2216684 + Quinidine in Cytochrome P450 (CYP)2C19 Poor Metabolizers (PM)
|
1530 nanograms*hours per milliliter (ng*h/mL)
Geometric Coefficient of Variation 34
|
—
|
SECONDARY outcome
Timeframe: Predose up to 120 hours post administration of quinidinePopulation: Participants who received at least 1 dose of LY2216684 and had evaluable LY2216684 plasma concentration data were included in the analysis.
Blood samples were collected prior to and up to 120 hours following coadministration of LY2216684 and quinidine on Day 11 (Period 2) for the measurement of LY2216684 plasma concentrations.
Outcome measures
| Measure |
LY2216684 (CYP2C19 Poor Metabolizers)
n=7 Participants
Participants were predicted to have a cytochrome P450 (CYP)2C19 poor metabolizer (PM) phenotype, as determined by genotyping analysis.
Period 1 (Days 1-7): a single, oral dose of 18 mg LY2216684 was administered on Day 1.
|
LY2216684 (CYP2C19 Extensive Metabolizers)
Participants were predicted to have a cytochrome P450 (CYP)2C19 extensive metabolizer (EM) phenotype, as determined by genotyping analysis.
Period 1 (Days 1-7): a single, oral dose of 18 mg LY2216684 administered on Day 1.
|
|---|---|---|
|
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2216684 + Quinidine in CYP2C19 Poor Metabolizers
|
66.9 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 23
|
—
|
SECONDARY outcome
Timeframe: Predose up to 120 hours post administration of quinidinePopulation: Participants who received at least 1 dose of LY2216684 and had evaluable LY2216684 plasma concentration data were included in the analysis.
Blood samples were collected prior to and up to 120 hours following coadministration of LY2216684 and quinidine on Day 11 (Period 2) for the measurement of LY2216684 plasma concentrations.
Outcome measures
| Measure |
LY2216684 (CYP2C19 Poor Metabolizers)
n=7 Participants
Participants were predicted to have a cytochrome P450 (CYP)2C19 poor metabolizer (PM) phenotype, as determined by genotyping analysis.
Period 1 (Days 1-7): a single, oral dose of 18 mg LY2216684 was administered on Day 1.
|
LY2216684 (CYP2C19 Extensive Metabolizers)
Participants were predicted to have a cytochrome P450 (CYP)2C19 extensive metabolizer (EM) phenotype, as determined by genotyping analysis.
Period 1 (Days 1-7): a single, oral dose of 18 mg LY2216684 administered on Day 1.
|
|---|---|---|
|
Pharmacokinetics: Time to Maximum Observed Plasma Concentration (Tmax) of LY2216684 + Quinidine in CYP2C19 Poor Metabolizers
|
3.00 hours
Interval 3.0 to 5.0
|
—
|
Adverse Events
LY2216684 (CYP2C19 Extensive and Poor Metabolizers)
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Quinidine (CYP2C19 Poor Metabolizers)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
LY2216684 + Quinidine (CYP2C19 Poor Metabolizers)
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 |
LY2216684 (CYP2C19 Extensive and Poor Metabolizers)
n=18 participants at risk
Participants were predicted to have a cytochrome P450 (CYP)2C19 extensive metabolizer (EM) or poor metabolizer (PM) phenotype, as determined by genotyping analysis.
Period 1 (Days 1-7): a single, oral dose of 18 milligrams (mg) LY2216684 administered on Day 1.
|
Quinidine (CYP2C19 Poor Metabolizers)
n=7 participants at risk
Participants were predicted to have a cytochrome P450 (CYP)2C19 poor metabolizer (PM) phenotype, as determined by genotyping analysis.
Period 2 (Days 8-11, prior to LY2216684 dose): 300 mg quinidine sulfate controlled release was administered orally, once daily on Days 8-11.
|
LY2216684 + Quinidine (CYP2C19 Poor Metabolizers)
n=7 participants at risk
Participants were predicted to have a cytochrome P450 (CYP)2C19 poor metabolizer (PM) phenotype, as determined by genotyping analysis.
Period 2 (Days 11-15, following LY2216684 dose): 300 mg quinidine sulfate controlled release was administered orally, once daily on Days 11-15. Additionally, a single, oral dose of 18 mg LY2216684 was administered on Day 11.
|
|---|---|---|---|
|
Eye disorders
Lacrimation increased
|
5.6%
1/18 • Number of events 1
|
0.00%
0/7
|
0.00%
0/7
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/18
|
14.3%
1/7 • Number of events 1
|
0.00%
0/7
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/18
|
0.00%
0/7
|
28.6%
2/7 • Number of events 2
|
|
Gastrointestinal disorders
Nausea
|
11.1%
2/18 • Number of events 2
|
0.00%
0/7
|
14.3%
1/7 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
22.2%
4/18 • Number of events 4
|
0.00%
0/7
|
0.00%
0/7
|
|
General disorders
Fatigue
|
5.6%
1/18 • Number of events 1
|
0.00%
0/7
|
0.00%
0/7
|
|
General disorders
Feeling hot
|
5.6%
1/18 • Number of events 1
|
0.00%
0/7
|
0.00%
0/7
|
|
General disorders
Vessel puncture site pain
|
5.6%
1/18 • Number of events 1
|
0.00%
0/7
|
0.00%
0/7
|
|
Infections and infestations
Upper respiratory tract infection
|
5.6%
1/18 • Number of events 1
|
0.00%
0/7
|
0.00%
0/7
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/18
|
0.00%
0/7
|
14.3%
1/7 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
16.7%
3/18 • Number of events 3
|
0.00%
0/7
|
14.3%
1/7 • Number of events 1
|
|
Nervous system disorders
Headache
|
0.00%
0/18
|
0.00%
0/7
|
14.3%
1/7 • Number of events 1
|
|
Psychiatric disorders
Social avoidant behaviour
|
0.00%
0/18
|
0.00%
0/7
|
14.3%
1/7 • Number of events 1
|
|
Renal and urinary disorders
Urinary hesitation
|
11.1%
2/18 • Number of events 2
|
0.00%
0/7
|
0.00%
0/7
|
|
Reproductive system and breast disorders
Testicular atrophy
|
11.1%
1/9 • Number of events 1
|
0.00%
0/5
|
0.00%
0/5
|
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