Trial Outcomes & Findings for A Study to Evaluate the Effect of LY2189265 on the Speed at Which Food and Drink Leaves the Stomach in Patients With Type 2 Diabetes Mellitus (NCT NCT01215968)
NCT ID: NCT01215968
Last Updated: 2014-10-07
Results Overview
After at least 8 hours fasting, participants received a radiolabeled breakfast containing technetium-99m-tin colloid (99mTc-tin colloid). After which serial anterior and posterior scintigraphy images were taken. Data presented are the time required for 50% of radioactivity to be emptied from stomach. The results presented are Geometric Least Squares (LS) Mean. LS Mean values were controlled for weeks.
COMPLETED
PHASE1
38 participants
Days 3, 10,17, 24 and 31
2014-10-07
Participant Flow
Participant milestones
| Measure |
Placebo
Participants received placebo on Week 1 and once-weekly doses of placebo on Weeks 2 to 5.
|
LY2189265
Participants received placebo on Week 1 and once-weekly doses of 1.5 milligram (mg) LY2189265 on Weeks 2 to 5.
|
|---|---|---|
|
Overall Study
STARTED
|
13
|
25
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
13
|
24
|
|
Overall Study
COMPLETED
|
11
|
18
|
|
Overall Study
NOT COMPLETED
|
2
|
7
|
Reasons for withdrawal
| Measure |
Placebo
Participants received placebo on Week 1 and once-weekly doses of placebo on Weeks 2 to 5.
|
LY2189265
Participants received placebo on Week 1 and once-weekly doses of 1.5 milligram (mg) LY2189265 on Weeks 2 to 5.
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
2
|
|
Overall Study
Protocol Violation
|
2
|
4
|
|
Overall Study
Not received study drug
|
0
|
1
|
Baseline Characteristics
A Study to Evaluate the Effect of LY2189265 on the Speed at Which Food and Drink Leaves the Stomach in Patients With Type 2 Diabetes Mellitus
Baseline characteristics by cohort
| Measure |
Placebo
n=13 Participants
Participants received placebo on Week 1 and once-weekly doses of placebo on Weeks 2 to 5.
|
LY2189265
n=25 Participants
Participants received placebo on Week 1 and once-weekly doses of 1.5 milligram (mg) LY2189265 on Weeks 2 to 5.
|
Total
n=38 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
52.0 years
STANDARD_DEVIATION 14.0 • n=5 Participants
|
58.9 years
STANDARD_DEVIATION 9.8 • n=7 Participants
|
56.5 years
STANDARD_DEVIATION 11.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
13 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
38 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
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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 Kingdom
|
13 participants
n=5 Participants
|
25 participants
n=7 Participants
|
38 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Days 3, 10,17, 24 and 31Population: All randomized participants who received study drug, a radiolabeled breakfast, and had scintigraphy images taken. Those who violated protocol were excluded.
After at least 8 hours fasting, participants received a radiolabeled breakfast containing technetium-99m-tin colloid (99mTc-tin colloid). After which serial anterior and posterior scintigraphy images were taken. Data presented are the time required for 50% of radioactivity to be emptied from stomach. The results presented are Geometric Least Squares (LS) Mean. LS Mean values were controlled for weeks.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received placebo on Week 1 and once-weekly doses of placebo on Weeks 2 to 5.
|
LY2189265
n=15 Participants
Participants received placebo on Week 1 and once-weekly doses of 1.5 milligram (mg) LY2189265 on Weeks 2 to 5.
|
LY2189265
Participants received placebo on Week 1 and once-weekly doses of 1.5 mg LY2189265 on Weeks 2 to 5.
|
|---|---|---|---|
|
Time Required for 50% of Radioactivity To Be Emptied From the Stomach by Scintigraphy
Day 3
|
1.44 hours
Interval 1.22 to 1.69
|
1.72 hours
Interval 1.43 to 2.06
|
—
|
|
Time Required for 50% of Radioactivity To Be Emptied From the Stomach by Scintigraphy
Day 10
|
1.41 hours
Interval 1.2 to 1.66
|
3.77 hours
Interval 3.15 to 4.51
|
—
|
|
Time Required for 50% of Radioactivity To Be Emptied From the Stomach by Scintigraphy
Day 17 (n=9, 14)
|
1.60 hours
Interval 1.36 to 1.89
|
3.32 hours
Interval 2.76 to 4.0
|
—
|
|
Time Required for 50% of Radioactivity To Be Emptied From the Stomach by Scintigraphy
Day 24 (n=9, 14)
|
1.47 hours
Interval 1.25 to 1.73
|
3.28 hours
Interval 2.72 to 3.94
|
—
|
|
Time Required for 50% of Radioactivity To Be Emptied From the Stomach by Scintigraphy
Day 31 (n=10, 13)
|
1.46 hours
Interval 1.24 to 1.71
|
3.15 hours
Interval 2.61 to 3.81
|
—
|
SECONDARY outcome
Timeframe: Days 3, 17 and 31Population: All randomized participants who received both study drug and immediate release metformin, and had PK data. Those who violated protocol were excluded.
Metformin was used as a secondary marker in the study to correlate the effect of LY2189265 on gastric emptying to the pharmacokinetics (PK) (measured as AUC) of concomitant medications. Participants taking metformin for treatment of Type 2 Diabetes Mellitus (T2DM) underwent PK assessments for metformin in parallel to their scintigraphy assessments for gastric emptying. AUC of metformin was calculated during one dosing interval.
Outcome measures
| Measure |
Placebo
n=6 Participants
Participants received placebo on Week 1 and once-weekly doses of placebo on Weeks 2 to 5.
|
LY2189265
n=12 Participants
Participants received placebo on Week 1 and once-weekly doses of 1.5 milligram (mg) LY2189265 on Weeks 2 to 5.
|
LY2189265
Participants received placebo on Week 1 and once-weekly doses of 1.5 mg LY2189265 on Weeks 2 to 5.
|
|---|---|---|---|
|
Area Under the Curve (AUC) of Metformin
Day 3
|
13600 nanograms*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 49 • Interval 11228.0 to 16824.0
|
13700 nanograms*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 40
|
—
|
|
Area Under the Curve (AUC) of Metformin
Day 17
|
14600 nanograms*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 47 • Interval 12523.0 to 18766.0
|
15300 nanograms*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 43
|
—
|
|
Area Under the Curve (AUC) of Metformin
Day 31 (n=6, 11)
|
14600 nanograms*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 47 • Interval 12941.0 to 19429.0
|
15800 nanograms*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 43
|
—
|
SECONDARY outcome
Timeframe: Days 3, 17 and 31Population: All randomized participants who received both study drug and immediate release metformin, and had pharmacokinetic (PK) data. Those who violated protocol were excluded.
Metformin was used as a secondary marker in the study to correlate the effect of LY2189265 on gastric emptying to the pharmacokinetics (PK) (measured as Cmax) of concomitant medications. Participants taking metformin for treatment of Type 2 Diabetes Mellitus (T2DM) underwent PK assessments for metformin in parallel to their scintigraphy assessments for gastric emptying.
Outcome measures
| Measure |
Placebo
n=6 Participants
Participants received placebo on Week 1 and once-weekly doses of placebo on Weeks 2 to 5.
|
LY2189265
n=12 Participants
Participants received placebo on Week 1 and once-weekly doses of 1.5 milligram (mg) LY2189265 on Weeks 2 to 5.
|
LY2189265
Participants received placebo on Week 1 and once-weekly doses of 1.5 mg LY2189265 on Weeks 2 to 5.
|
|---|---|---|---|
|
Maximum Concentration (Cmax) of Metformin
Day 31 (n=6, 11)
|
1770 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 46
|
1680 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 44
|
—
|
|
Maximum Concentration (Cmax) of Metformin
Day 17
|
1690 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 48
|
1500 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 53
|
—
|
|
Maximum Concentration (Cmax) of Metformin
Day 3
|
1610 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 48
|
1690 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 47
|
—
|
SECONDARY outcome
Timeframe: Days 3, 17 and 31Population: All randomized participants who received both study drug and immediate release metformin, and had pharmacokinetic (PK) data. Those who violated protocol were excluded.
Metformin was used as a secondary marker in the study to correlate the effect of LY2189265 on gastric emptying to the pharmacokinetics (PK) (measured as Tmax) of concomitant medications. Participants taking metformin for treatment of Type 2 Diabetes Mellitus (T2DM) underwent PK assessments for metformin in parallel to their scintigraphy assessments for gastric emptying.
Outcome measures
| Measure |
Placebo
n=6 Participants
Participants received placebo on Week 1 and once-weekly doses of placebo on Weeks 2 to 5.
|
LY2189265
n=12 Participants
Participants received placebo on Week 1 and once-weekly doses of 1.5 milligram (mg) LY2189265 on Weeks 2 to 5.
|
LY2189265
Participants received placebo on Week 1 and once-weekly doses of 1.5 mg LY2189265 on Weeks 2 to 5.
|
|---|---|---|---|
|
Time to Maximum Concentration (Tmax) of Metformin
Day 3
|
1.00 hour
Interval 1.0 to 2.03
|
2.02 hour
Interval 1.0 to 4.1
|
—
|
|
Time to Maximum Concentration (Tmax) of Metformin
Day 17
|
2.02 hour
Interval 1.02 to 8.0
|
2.05 hour
Interval 0.96 to 4.02
|
—
|
|
Time to Maximum Concentration (Tmax) of Metformin
Day 31 (n=6, 11)
|
1.53 hour
Interval 0.98 to 4.0
|
2.02 hour
Interval 1.0 to 4.03
|
—
|
SECONDARY outcome
Timeframe: Baseline through 5 weeksPopulation: All enrolled participants who received at least one dose of study drug.
Adverse events (AEs) were considered clinically significant effects. A summary of serious adverse events (SAEs) and other nonserious AEs are located in the Reported Adverse Event section.
Outcome measures
| Measure |
Placebo
n=13 Participants
Participants received placebo on Week 1 and once-weekly doses of placebo on Weeks 2 to 5.
|
LY2189265
n=25 Participants
Participants received placebo on Week 1 and once-weekly doses of 1.5 milligram (mg) LY2189265 on Weeks 2 to 5.
|
LY2189265
n=24 Participants
Participants received placebo on Week 1 and once-weekly doses of 1.5 mg LY2189265 on Weeks 2 to 5.
|
|---|---|---|---|
|
Number of Participants With Clinically Significant Effects
SAEs
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Clinically Significant Effects
Other nonserious AEs
|
7 participants
|
11 participants
|
20 participants
|
Adverse Events
Placebo
Placebo (Week 1)
LY2189265
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=13 participants at risk
Participants received placebo on Week 1 and once-weekly doses of placebo on Weeks 2 to 5.
|
Placebo (Week 1)
n=25 participants at risk
Participants received placebo on Week 1 and went on to receive once-weekly doses of 1.5 milligram (mg) LY2189265 on Weeks 2 to 5.
|
LY2189265
n=24 participants at risk
Participants received placebo on Week 1 and once-weekly doses of 1.5 mg LY2189265 on Weeks 2 to 5.
|
|---|---|---|---|
|
Eye disorders
Eye irritation
|
7.7%
1/13 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/13
|
0.00%
0/25
|
12.5%
3/24 • Number of events 3
|
|
Gastrointestinal disorders
Abdominal distension
|
7.7%
1/13 • Number of events 1
|
0.00%
0/25
|
16.7%
4/24 • Number of events 8
|
|
Gastrointestinal disorders
Abdominal pain upper
|
15.4%
2/13 • Number of events 2
|
0.00%
0/25
|
8.3%
2/24 • Number of events 2
|
|
Gastrointestinal disorders
Diarrhoea
|
7.7%
1/13 • Number of events 1
|
8.0%
2/25 • Number of events 2
|
29.2%
7/24 • Number of events 19
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/13
|
4.0%
1/25 • Number of events 1
|
29.2%
7/24 • Number of events 18
|
|
Gastrointestinal disorders
Eructation
|
7.7%
1/13 • Number of events 1
|
0.00%
0/25
|
20.8%
5/24 • Number of events 7
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/13
|
0.00%
0/25
|
12.5%
3/24 • Number of events 6
|
|
Gastrointestinal disorders
Nausea
|
23.1%
3/13 • Number of events 4
|
4.0%
1/25 • Number of events 1
|
50.0%
12/24 • Number of events 25
|
|
Gastrointestinal disorders
Toothache
|
7.7%
1/13 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
|
Gastrointestinal disorders
Vomiting
|
7.7%
1/13 • Number of events 1
|
0.00%
0/25
|
25.0%
6/24 • Number of events 11
|
|
General disorders
Injection site pain
|
7.7%
1/13 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
|
General disorders
Vessel puncture site haematoma
|
0.00%
0/13
|
8.0%
2/25 • Number of events 2
|
8.3%
2/24 • Number of events 4
|
|
Infections and infestations
Bronchitis
|
7.7%
1/13 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
|
Infections and infestations
Lower respiratory tract infection
|
7.7%
1/13 • Number of events 1
|
0.00%
0/25
|
4.2%
1/24 • Number of events 1
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/13
|
4.0%
1/25 • Number of events 1
|
16.7%
4/24 • Number of events 4
|
|
Injury, poisoning and procedural complications
Limb injury
|
7.7%
1/13 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
|
Injury, poisoning and procedural complications
Procedural nausea
|
7.7%
1/13 • Number of events 5
|
4.0%
1/25 • Number of events 1
|
0.00%
0/24
|
|
Metabolism and nutrition disorders
Decreased appetite
|
7.7%
1/13 • Number of events 1
|
0.00%
0/25
|
33.3%
8/24 • Number of events 12
|
|
Metabolism and nutrition disorders
Increased appetite
|
15.4%
2/13 • Number of events 3
|
0.00%
0/25
|
4.2%
1/24 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/13
|
0.00%
0/25
|
12.5%
3/24 • Number of events 5
|
|
Nervous system disorders
Dizziness
|
7.7%
1/13 • Number of events 1
|
8.0%
2/25 • Number of events 2
|
16.7%
4/24 • Number of events 4
|
|
Nervous system disorders
Headache
|
15.4%
2/13 • Number of events 3
|
16.0%
4/25 • Number of events 4
|
20.8%
5/24 • Number of events 7
|
|
Nervous system disorders
Lethargy
|
0.00%
0/13
|
0.00%
0/25
|
12.5%
3/24 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
7.7%
1/13 • Number of events 1
|
4.0%
1/25 • Number of events 1
|
8.3%
2/24 • Number of events 2
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60