A Study of the Effect of LY2189265 on Two Blood Pressure Drugs

NCT01324388 | Completed Phase 1 Results

• 2 other identifiers: 11552H9X-MC-GBCO
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is twofold:

1. 1.To evaluate the effect of LY2189265 on how the body absorbs a blood pressure lowering drug (lisinopril) in participants with high blood pressure who are currently taking lisinopril.
2. 2.To evaluate the effect of LY2189265 on heart rate and blood pressure in healthy volunteers when taken with a Beta-blocker drug (metoprolol).

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (4)

• Pharmacokinetics, Area Under the Concentration Curve (AUC) of Lisinopril

  Day -1, Day 3, Day 24 of Part 1

• Pharmacokinetics, Maximum Concentration (Cmax) of Lisinopril

  Day -1, Day 3, Day 24 in Part 1

• Mean, 24-hour Heart Rate (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Metoprolol

  Day -1, Day 4, Day 7 of Treatment 2 in Part 2

• Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Metoprolol

  Day -1, Day 4, Day 7 of Treatment 2 in Part 2

Secondary Outcomes (4)

• Mean, 24-hour Heart Rate (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril

  Day -1, Day 3, Day 24 of Part 1

• Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril

  Day -1, Day 3, Day 24 of Part 1

• Pharmacokinetics, Area Under the Concentration Curve (AUC) of Metoprolol When Administered With LY2189265

  Day 4 and Day 7 of Treatment 2 in Part 2

• Pharmacokinetics, Maximum Concentration (Cmax) of Metoprolol When Administered With LY2189265

  Day 4 and Day 7 of Treatment 2 in Part 2

Study Arms (4)

LY2189265 + Lisinopril

EXPERIMENTAL

LY2189265 (dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), on Days 1, 8, 15, and 22 of Part 1 of the study. Lisinopril: Dose as prescribed by participant's established course of therapy, oral, daily dosing throughout Part 1 of the study.

Biological: LY2189265; Drug: Lisinopril

Placebo + Lisinopril

PLACEBO COMPARATOR

Placebo: 1.5 milligrams (mg), subcutaneous (SC), on Days 1, 8, 15, and 22 of Part 1 of the study. Lisinopril: Dose as prescribed by participant's established course of therapy, oral, daily dosing throughout Part 1 of the study.

Drug: Lisinopril; Drug: Placebo

LY2189265 (Treatment 1)/Metoprolol + LY2189265 (Treatment 2)

EXPERIMENTAL

LY2189265 (dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), on Day 1 of Treatment 1 and on Day 5 of Treatment 2 in Part 2 of the study. Metoprolol: 100 mg, oral, on Days 1 through 7 of Treatment 2 in Part 2 of the study. There was a washout period of at least 21 days between the LY2189265 and metoprolol doses of each treatment period (Day 1 of Treatment 1 to Day 1 of Treatment 2 in Part 2 of the study).

Biological: LY2189265; Drug: Metoprolol

Metoprolol + LY2189265 (Treatment 2)/LY2189265 (Treatment 1)

EXPERIMENTAL

LY2189265 (dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), on Day 5 of Treatment 2 and on Day 1 of Treatment 1 in Part 2 of the study. Metoprolol: 100 mg, oral, on Days 1 through 7 of Treatment 2 in Part 2 of the study. There was a washout period of at least 21 days between the LY2189265 and metoprolol doses of each treatment period (Day 7 of Treatment 2 to Day 1 of Treatment 1 in Part 2 of the study).

Biological: LY2189265; Drug: Metoprolol

Interventions

LY2189265 BIOLOGICAL

Administered subcutaneously

Also known as: dulaglutide

LY2189265 (Treatment 1)/Metoprolol + LY2189265 (Treatment 2); LY2189265 + Lisinopril; Metoprolol + LY2189265 (Treatment 2)/LY2189265 (Treatment 1)

Metoprolol DRUG

Administered orally

LY2189265 (Treatment 1)/Metoprolol + LY2189265 (Treatment 2); Metoprolol + LY2189265 (Treatment 2)/LY2189265 (Treatment 1)

Lisinopril DRUG

Administered orally

LY2189265 + Lisinopril; Placebo + Lisinopril

Placebo DRUG

Administered subcutaneously

Placebo + Lisinopril

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male participants: agree to use a reliable method of birth control during the study and for 3 months following the last dose of the investigational product
• Female participants: women not of child-bearing potential due to menopause or surgical sterilization (at least 6 weeks post surgical bilateral oophorectomy, hysterectomy or tubal ligation) confirmed by medical history
• Have a body mass index (BMI) of 18.5 to 40.0 kilograms/square meter (kg/m\^2), inclusive at the time of screening
• Have clinical laboratory test results within normal reference range for the population or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator
• Have venous access sufficient to allow for blood sampling as per the protocol
• Are reliable and willing to make themselves available for the duration of the study and are willing to follow study restrictions
• Have given written informed consent on an informed consent form (ICF) approved by Lilly and the corresponding ethics committee (EC) or ethical review board (ERB) governing the site
• Part 1 only:
• Have controlled mild to moderate hypertension (supine blood pressure \[BP\] less than or equal to 140/90 millimeter of mercury (mm Hg) at screening, or results with acceptable deviations that are judged not to be clinically significant by the investigator).
• Males and females with stable medical problems (including Type 2 Diabetes Mellitus \[T2DM\]) that, in the investigator's opinion, will not significantly alter the disposition of the drug, will not place the participant at increased risk by participating in the study, and will not interfere with interpretation of the data may be included
• Have been on oral antihypertensive medication (lisinopril daily \[QD\]) for at least 3 months prior to screening, have been on a stable dose for at least 1 month prior to screening, and are, in the investigator's opinion, able to safely adhere to a QD morning dosing regimen. Additional medication may be permitted as indicated
• T2DM Participants (Part 1 only):
• Have T2DM controlled with diet or exercise alone or stable on a single oral agent antihyperglycemic medication (metformin, sulfonylureas, repaglinide, nateglinide, acarbose \[or other disaccharidase inhibitors\] or thiazolidinediones) for at least 3 weeks (3 months for thiazolidinediones) prior to admission
• Have a hemoglobin A1c (HbA1c) value of 6.0% to 9.5% at screening or within 4 weeks prior to screening
• Clinical laboratory test results within normal range or deemed clinically insignificant by the investigator. Abnormalities of serum glucose, serum lipids, urinary glucose, and urinary protein consistent with T2DM are acceptable

You may not qualify if:

• Are currently enrolled in, have completed or discontinued within the last 30 days from, a clinical trial involving an investigational product; or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
• Have known allergies to Glucagon-like peptide-1 (GLP-1)-related compounds, including LY2189265, or any components of the formulation
• Are participants who have previously completed or withdrawn from this study, or have taken part in any other study investigating LY2189265 or GLP-1-related compounds within the last 3 months
• Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study
• Have a history or presence of gastrointestinal disorder (including pancreatitis \[history of chronic pancreatitis or idiopathic acute pancreatitis\] or gall bladder disease) or gastrointestinal disease that impacts gastric emptying (GE) (e.g. gastric bypass surgery, pyloric stenosis) or could be aggravated by GLP-1 analogs (for example; esophageal reflux). Participants having had cholecystectomy (removal of gall bladder) in the past with no further sequelae, may be included in the study at the discretion of the screening physician
• Have a history or presence of thyroid disease, unless have been on a stable dose of thyroxine replacement therapy for at least 1 month
• Show history or evidence of significant active neuropsychiatric disease
• Have personal or family history of medullary thyroid cancer (MTC) or a genetic condition that predisposes to MTC
• Regularly use known drugs of abuse and/or show positive findings on urinary drug screening
• Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies
• Show evidence of hepatitis C and/or positive hepatitis C antibody
• Show evidence of hepatitis B and/or positive hepatitis B surface antigen
• Intend to start new concomitant medication during the study, including over-the-counter and herbal medication, use drugs that directly reduce gastrointestinal motility or who regularly use systemic corticosteroids, or potent, inhaled, or intranasal steroids known to have a high rate of systemic absorption
• Have donated more than 500 milliliters (mL) of blood within the month prior to screening
• Have a nondominant arm circumference of greater than 42 centimeters (cm)

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (3)

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.

Honolulu, Hawaii, 96813, United States

Location

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.

Evansville, Indiana, 47710, United States

Location

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.

Dallas, Texas, 75247, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

dulaglutide; Metoprolol; Lisinopril

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2011
• First Posted: March 29, 2011
• Study Start: March 1, 2011
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: October 8, 2014
• Results First Posted: October 8, 2014

Record last verified: 2014-10

Locations

US (3)