A Study of LY2409021 on Blood Pressure and Pulse Rate in Participants With Type 2 Diabetes Mellitus

Type 2 Diabetes Mellitus Clinical Trial

Official title:

The Effect of LY2409021 on Blood Pressure and Pulse Rate, as Assessed by Ambulatory Blood Pressure Monitoring, in Subjects With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02091362
• Other study ID #: 15261
• Secondary ID: I1R-MC-GLDI2013-
• Status: Completed
• Phase: Phase 2
• Start date: March 2014
• Est. completion date: January 2015

Study information

• Verified date: July 2018
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of the trial is to determine the effect of a study drug known as LY2409021 on blood pressure and pulse rate in participants with type 2 diabetes mellitus (T2DM) when compared to placebo. The study has two periods. Each participant will receive LY2409021 or placebo in each period. At least 4 weeks will pass between periods. The study will last about 23 weeks for each participant. Participants may remain on stable dose metformin, as prescribed by their personal physician.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 270
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have type 2 diabetes mellitus (according to the World Health Organization diagnostic criteria) and use diet and exercise alone or in combination with a stable dose of metformin ( >/=1000 mg/day [or <1000 mg, if documented intolerance to 1000 mg or higher dosages] immediate-release metformin or extended-release metformin for at least 2 months before screening).

• Have glycated hemoglobin (HbA1c) values >/=6.5% and </=8.5%, as determined by the central laboratory at screening.

• Have mean blood pressures >90/60 millimeters of mercury (mm Hg) and <140/90 mm Hg at screening.

• If being treated for hypertension, are taking 3 or fewer antihypertensive medications and have been taking stable doses of the same medications for at least 1 month before screening.

• Stable body weights (±5%) for >/=3 months before screening.

• Body mass indexes >/=20 kilograms/meters squared (kg/m²) and <40 kg/m².

• In the investigator's opinion, are well motivated, capable, and willing to:

• Reliably administer the oral study drug once daily;

• Maintain a study diary;

• Perform self-monitored blood glucose testing; and

• Wear an ambulatory blood pressure monitoring device for at least 24 hours (on multiple occasions).

• Are women not of child-bearing potential due to:

• Surgical sterilization, hysterectomy, or bilateral oophorectomy (at least 6 weeks postsurgery) or tubal ligation (confirmed by medical history); or

• Menopause. Women with an intact uterus are deemed menopausal if they have a cessation of menses for at least 1 year with follicle stimulating hormone >40 milli-international units per milliliter (mIU/mL), are not taking hormones or oral contraceptives within 1 year, and are otherwise healthy.

• Males who are sexually active and/or have partners of child-bearing age must use reliable methods of birth control during the study and until 3 months after the last doses of study medication. These requirements do not apply if a participant or his partner has been surgically sterilized or is not between menarche and 1 year postmenopausal.

Exclusion Criteria:

• Have severe gastrointestinal disease that may significantly affect gastric emptying or motility.

• Previous histories or active diagnoses of pancreatitis.

• Acute or chronic hepatitis, signs or symptoms of any other liver disease, or alanine aminotransferase (ALT) level greater than 2.5 times the upper limit of normal (ULN).

• Elevated total bilirubin (greater than 2 times ULN), clinically suspicious signs or symptoms of cirrhosis or history of cirrhosis.

• Mean resting pulse rate (PR) less than 60 beats per minute (bpm) or greater than 100 bpm.

• Current diagnosis or personal history of neuroendocrine tumors, family history of any type of multiple endocrine neoplasia, or Von Hippel-Lindau disease.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• LY2409021
Administered orally
• Placebo
Administered orally
• Metformin
Administered as background therapy.

Locations

Country	Name	City	State
Czechia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Holesov
Czechia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Krnov
Czechia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Pardubice
Czechia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Prague
Mexico	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Coatzacoalcos
Mexico	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Guadalajara
Mexico	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Monterrey
Mexico	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Monterrey
Poland	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Gdansk
Poland	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lodz
Poland	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lublin
Poland	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Poznan
Poland	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Szczecin
Puerto Rico	Manati Center for Clinical Research Inc	Manati
Puerto Rico	Consultorio Medico	San Juan
United States	Advanced Clinical Research Institute	Anaheim	California
United States	Maine Research Associates	Auburn	Maine
United States	Cedar-Crosse Research Center	Chicago	Illinois
United States	Alzohaili Medical Consultants	Dearborn	Michigan
United States	Berma Research	Fort Lauderdale	Florida
United States	Midwest Institute for Clinical Research	Indianapolis	Indiana
United States	East Coast Clinical Research	Jacksonville	Florida
United States	National Research Institute	Los Angeles	California
United States	L-Marc Research Center	Louisville	Kentucky
United States	Suncoast Research Group, LLC	Miami	Florida
United States	Manhattan Medical Research	New York	New York
United States	Artemis Institute for Clinical Research	San Diego	California
United States	Premier Research	Trenton	New Jersey
United States	Orange County Research Center	Tustin	California
United States	University Clinical Investigators, Inc.	Tustin	California

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Czechia,  Mexico,  Poland,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to 6 Weeks in Mean 24-Hour Systolic Blood Pressure	Systolic blood pressure obtained from Ambulatory Blood Pressure Monitoring (ABPM).	Baseline, 6 Weeks
Secondary	Change From Baseline to 6 Weeks in Mean 24-Hour Diastolic Blood Pressure	Diastolic blood pressure obtained from Ambulatory Blood Pressure Monitoring (ABPM). LS Mean of treatment differences, adjusted for country, diagnosis of hypertension, sequence, treatment, period, time within period, treatment by time within period interaction, and the baseline measurement as covariate.	Baseline, 6 Weeks
Secondary	Change From Baseline to 6 Weeks in Mean 24-Hour, Daytime, and Nighttime Peripheral Pulse Rate	Pulse rate obtained from Ambulatory Blood Pressure Monitoring (ABPM). LS Mean of treatment differences, adjusted for country, diagnosis of hypertension, sequence, treatment, period, time within period, treatment by time within period interaction, and the baseline measurement as covariate.	Baseline, 6 Weeks
Secondary	Change From Baseline to 6 Weeks in Mean 24-Hour, Daytime, and Nighttime Pulse Pressures	Pulse Pressures obtained from Ambulatory Blood Pressure Monitoring (ABPM). LS Mean of treatment differences, adjusted for country, diagnosis of hypertension, sequence, treatment, period, time within period, treatment by time within period interaction, and the baseline measurement as covariate.	Baseline, 6 Weeks
Secondary	Change From Baseline to 6 Weeks in Mean 24-Hour, Daytime, and Nighttime Mean Arterial Pressures (MAP)	Mean Arterial Pressures obtained from Ambulatory Blood Pressure Monitoring (ABPM). LS Mean of treatment differences, adjusted for country, diagnosis of hypertension, sequence, treatment, period, time within period, treatment by time within period interaction, and the baseline measurement as covariate.	Baseline, 6 Weeks
Secondary	Change From Baseline in Hemoglobin A1c (HbA1c)	LS Mean of treatment differences, adjusted for country, diagnosis of hypertension, sequence, treatment, period, time within period, treatment by time within period interaction, and the baseline measurement as covariate.	Baseline, 6 Weeks
Secondary	Population Pharmacokinetics: Apparent Clearance of LY2409021	Population pharmacokinetic parameter apparent clearance (CL/F) is the apparent volume of the body fluid cleared of the drug per unit of time and was estimated by modeling of LY2409021 plasma concentration data from all LY2409021 groups.	Days 7, 21, 42, 70, 77, 91, 112, 140; 15 minute Predose and Days 7 and 77: 1 hour Postdose.
Secondary	Population Pharmacokinetics: Apparent Volume of Distribution of LY2409021	Population pharmacokinetic parameter, apparent volume of distribution (V/F) is a theoretical volume that a drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it currently is in blood plasma. Apparent volume of distribution (V/F) was estimated by modeling of LY2409021 plasma concentration data from all LY2409021 groups.	Days 7, 21, 42, 70, 77, 91, 112, 140; Predose and Days 7 and 77: 1 hour Postdose.