A Study of LY2409021 in Participants With Type 2 Diabetes Mellitus

A Phase 2, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Efficacy of LY2409021 Compared to Sitagliptin in Subjects With Type 2 Diabetes Mellitus

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02111096

Enrollment

174

Registered

2014-04-10

Start date

2014-04-30

Completion date

2015-09-30

Last updated

2019-10-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes Mellitus, Type 2

Brief summary

The intent of this study is to assess the safety of LY2409021 in participants with Type 2 diabetes mellitus taking metformin and sulfonylurea as prescribed by their personal physician. The study treatment is expected to last 12 months (52 weeks).

Interventions

DRUGLY2409021

Administered orally

DRUGSitagliptin

Administered orally

DRUGPlacebo

Administered orally

DRUGMetformin

Administered orally

DRUGSulfonylurea

Administered orally

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 79 Years

Healthy volunteers

Inclusion criteria

* Have been treated with a stable dose of metformin for at least 3 months and have been treated with an optimally effective and stable dose of an sulfonylurea for at least 6 months prior to screening. * HbA1c value between 7.0% and 10.0%, inclusive. * Body mass index (BMI) between 20 and 45 kilograms/square meter (kg/m\^2), inclusive.

Exclusion criteria

* Known type 1 diabetes mellitus. * More than 1 episode of severe hypoglycemia within 6 months prior to screening. * Two or more emergency room visits or hospitalizations due to poor glucose control in the 6 months prior to screening. * Severe gastrointestinal disease that may significantly impact gastric emptying or motility or having undergone gastric bypass or gastric banding surgery. * Previous history or active diagnosis of pancreatitis. * Positive hepatitis B surface antigen or hepatitis C antibody. * Clinical signs or symptoms of liver disease, or hepatic aminotransferases (aminotransferase or alanine aminotransferase) greater than 2.0× upper limit of normal (ULN) or elevated alkaline phosphatase (greater than ULN) unrelated to bone metabolic disease. * Elevated total bilirubin level (greater than ULN), clinically suspicious signs/symptoms of cirrhosis or history of cirrhosis. * Current diagnosis, personal history of neuroendocrine tumors, family history of any type of multiple endocrine neoplasia (MEN), or Von Hippel-Lindau. * Contraindications for magnetic resonance imaging.

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline to 6 Months in Hepatic Fat Fraction	Baseline, 6 months	The hepatic fat fraction (HFF) was calculated by a core imaging laboratory from noncontrast magnetic resonance imaging (MRI) of the liver. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (\<=8.0%, \>8.0%), visit, baseline score, and treatment-by-visit.

Secondary

Measure	Time frame	Description
Number of Participants With Hepatobiliary Adverse Events of Special Interest (AESI)	Baseline, 6 months	Number of participants with ALT or AST greater than 3 times the upper limit of normal at a post-baseline visit. A summary of other non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Change From Baseline to 6 Months in Fasting Lipids Levels	Baseline, 6 months	Lipid values (cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides) assessed by a central laboratory. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (\<=8.0%, \>8.0%), visit, baseline score, and treatment-by-visit.
Change From Baseline to 6 Months in Fasting Blood Glucagon	Baseline, 6 months	Glucagon values assessed by a central laboratory. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (\<=8.0%, \>8.0%), visit, baseline score, and treatment-by-visit.
Change From Baseline to 6 Months in Body Weight	Baseline, 6 months	Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (\<=8.0%, \>8.0%), visit, baseline score, and treatment-by-visit.
Change From Baseline to 6 Months in Hemoglobin A1c (HbA1c)	Baseline, 6 months	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, visit, baseline score, and treatment-by-visit.
Change From Baseline to 6 Months in Fasting Plasma Glucose	Baseline, 6 months	Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (\<=8.0%, \>8.0%), visit, baseline score, and treatment-by-visit.
Change From Baseline to 6 Months in Alanine Aminotransferase Levels	Baseline, 6 months	Alanine aminotransferase (ALT) assessed by a central laboratory. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (\<=8.0%, \>8.0%), visit, baseline score, and treatment-by-visit.
Change From Baseline to 6 Months in Pulse Rate	Baseline, 6 months	Seated pulse rate was measured in triplicate throughout the study. At each visit, all available pulse measurements for a subject were averaged to provide the pulse for that visit. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (\<=8.0%, \>8.0%), visit, baseline score, and treatment-by-visit.
Change From Baseline to 6 Months in 7-Point Self-Monitoring of Blood Glucose (SMBG)	Baseline, 6 months	7-point profile consists of pre-meal and 2-hour postprandial SMBG measurements for the morning, midday, and evening meals in 1 day and at 3 AM (nocturnal blood glucose measurement). Pre-meal measurements were taken before the subject began eating the meal. Participants recorded their glucose measurements in their study diaries.
Population Pharmacokinetics: Apparent Clearance of LY2409021	Day 1 Month 1, 3, 6, 9, predose, 1 hour postdose,	Reported as a Population Estimate with % Standard Errors of Estimation (SEE), 5th-95th confidence interval.
Population Pharmacokinetics: Apparent Volume of Distribution of LY2409021	Day 1 Month 1, 3, 6, 9, predose, 1 hour postdose,	—
Rate of Hypoglycemic Events Adjusted Per 30 Days	Baseline through 6 months	Documented symptomatic hypoglycemia, an event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration \<=70 mg/dL (\<=39 mmol/L),is presented. Rate: (30 days) is calculated as: (number of episodes during the time period divided by the number of days during the time period) multiplied by 30.
Number of Participants With Hypoglycemic Events	Baseline through 6 months	Documented symptomatic hypoglycemia, an event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration \<=70 mg/dL (\<=39 mmol/L), is presented. The number of subjects with an event are subjects who had at least one episode of documented symptomatic hypoglycemia during the time period.
Change From Baseline to 6 Months in Blood Pressure	Baseline, 6 months	Seated systolic blood pressure (SBP) and seated diastolic blood pressure (DBP) were measured in triplicate throughout the study. At each visit, all available blood pressure measurements for a subject were averaged to provide the blood pressure for that visit. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (\<=8.0%, \>8.0%), visit, baseline score, and treatment-by-visit.

Countries

Greece, Puerto Rico, Taiwan, United States

Participant flow

Participants by arm

Arm	Count
LY2409021 20 milligrams (mg) LY2409021 given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	65
Sitagliptin 100 mg sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	41
Placebo Placebo matching LY2409021 and sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	68
Total	174

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	4	1	2
Overall Study	Lost to Follow Up	1	1	1
Overall Study	Non-Compliance with Study Drug	1	1	0
Overall Study	Physician Decision	0	1	0
Overall Study	Protocol Violation	1	0	1
Overall Study	Terminated by Sponsor	53	35	54
Overall Study	Withdrawal by Subject	4	2	8

Baseline characteristics

Characteristic	Sitagliptin	Placebo	LY2409021	Total
Age, Continuous	57.1 years STANDARD_DEVIATION 8.99	57.8 years STANDARD_DEVIATION 8.21	56.9 years STANDARD_DEVIATION 8.33	57.3 years STANDARD_DEVIATION 8.41
Ethnicity (NIH/OMB) Hispanic or Latino	19 Participants	42 Participants	30 Participants	91 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants	25 Participants	34 Participants	80 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants	1 Participants	1 Participants	3 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	2 Participants	5 Participants	4 Participants	11 Participants
Race (NIH/OMB) Black or African American	6 Participants	11 Participants	14 Participants	31 Participants
Race (NIH/OMB) More than one race	2 Participants	1 Participants	5 Participants	8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	31 Participants	51 Participants	42 Participants	124 Participants
Region of Enrollment Greece	4 Participants	6 Participants	6 Participants	16 Participants
Region of Enrollment Puerto Rico	5 Participants	13 Participants	8 Participants	26 Participants
Region of Enrollment Taiwan	1 Participants	4 Participants	3 Participants	8 Participants
Region of Enrollment United States	31 Participants	45 Participants	48 Participants	124 Participants
Sex: Female, Male Female	10 Participants	31 Participants	24 Participants	65 Participants
Sex: Female, Male Male	31 Participants	37 Participants	41 Participants	109 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	26 / 65	22 / 41	21 / 68
serious Total, serious adverse events	5 / 65	5 / 41	1 / 68

Outcome results

Primary

Change From Baseline to 6 Months in Hepatic Fat Fraction

The hepatic fat fraction (HFF) was calculated by a core imaging laboratory from noncontrast magnetic resonance imaging (MRI) of the liver. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (\<=8.0%, \>8.0%), visit, baseline score, and treatment-by-visit.