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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01324388
First received: March 25, 2011
Last updated: October 3, 2014
Last verified: October 2014
  Purpose

The purpose of this study is twofold:

  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. To evaluate the effect of LY2189265 on heart rate and blood pressure in healthy volunteers when taken with a Beta-blocker drug (metoprolol).

In Part 1, participants will receive four weekly injections of LY2189265 with continued use of normal lisinopril therapy.

Part 2 is a cross-over study design. Participants will receive a single injection of LY2189265 in one period, and seven daily doses of metoprolol and a single injection of LY2189265 in another period.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Biological: LY2189265
Drug: Metoprolol
Drug: Lisinopril
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Pharmacokinetic and Pharmacodynamic Effect of LY2189265 on Lisinopril in Subjects With Hypertension and Metoprolol in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Pharmacokinetics, Area Under the Concentration Curve (AUC) of Lisinopril [ Time Frame: Day -1, Day 3, Day 24 of Part 1 ] [ Designated as safety issue: No ]
  • Pharmacokinetics, Maximum Concentration (Cmax) of Lisinopril [ Time Frame: Day -1, Day 3, Day 24 in Part 1 ] [ Designated as safety issue: No ]
  • Mean, 24-hour Heart Rate (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Metoprolol [ Time Frame: Day -1, Day 4, Day 7 of Treatment 2 in Part 2 ] [ Designated as safety issue: Yes ]
  • Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Metoprolol [ Time Frame: Day -1, Day 4, Day 7 of Treatment 2 in Part 2 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Mean, 24-hour Heart Rate (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril [ Time Frame: Day -1, Day 3, Day 24 of Part 1 ] [ Designated as safety issue: Yes ]
  • Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril [ Time Frame: Day -1, Day 3, Day 24 of Part 1 ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics, Area Under the Concentration Curve (AUC) of Metoprolol When Administered With LY2189265 [ Time Frame: Day 4 and Day 7 of Treatment 2 in Part 2 ] [ Designated as safety issue: No ]
  • Pharmacokinetics, Maximum Concentration (Cmax) of Metoprolol When Administered With LY2189265 [ Time Frame: Day 4 and Day 7 of Treatment 2 in Part 2 ] [ Designated as safety issue: No ]

Enrollment: 51
Study Start Date: March 2011
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LY2189265 + Lisinopril

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
Administered subcutaneously
Other Name: dulaglutide
Drug: Lisinopril
Administered orally
Placebo Comparator: Placebo + Lisinopril

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
Administered orally
Drug: Placebo
Administered subcutaneously
Experimental: LY2189265 (Treatment 1)/Metoprolol + LY2189265 (Treatment 2)

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
Administered subcutaneously
Other Name: dulaglutide
Drug: Metoprolol
Administered orally
Experimental: Metoprolol + LY2189265 (Treatment 2)/LY2189265 (Treatment 1)

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
Administered subcutaneously
Other Name: dulaglutide
Drug: Metoprolol
Administered orally

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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

Part 2 only:

• Are overtly healthy, as determined by medical history and physical examination

Exclusion Criteria:

  • 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)
  • Have an average weekly alcohol intake that exceeds 21 units per week (males up to age 65) and 14 units per week (males over 65 and females), or are unwilling to stop alcohol consumption from 48 hours before each admission until discharge from the unit, and to limit alcohol intake to a maximum of 2 units/day on all other days from screening through 48 hours prior to the follow-up visit. (1 unit = 12 ounces [oz] or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits)
  • Are participants who, in the opinion of the investigator, are in any way unsuitable to participate in the study

Part 1 only:

• Have any medical conditions, medical history or are taking any medication which are contraindicated within the lisinopril product information leaflet

Part 2 only:

  • Intend to use over-the-counter medication (with the exception of paracetamol and/or antacids) within 7 days prior to dosing or prescription medication (with the exception of vitamin/mineral supplements and/or hormone replacement therapy and/or thyroid replacement therapy) within 14 days prior to dosing of the investigational product
  • Have any medical conditions, medical history or are taking any medication which are contraindicated within the metoprolol product information leaflet
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01324388

Locations
United States, Hawaii
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, United States, 96813
United States, Indiana
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, United States, 47710
United States, Texas
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, United States, 75247
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01324388     History of Changes
Other Study ID Numbers: 11552, H9X-MC-GBCO
Study First Received: March 25, 2011
Results First Received: October 3, 2014
Last Updated: October 3, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Lisinopril
Metoprolol
Metoprolol succinate
Adrenergic Agents
Adrenergic Antagonists
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Angiotensin-Converting Enzyme Inhibitors
Anti-Arrhythmia Agents
Antihypertensive Agents
Autonomic Agents
Cardiotonic Agents
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors
Protective Agents
Sympatholytics
Therapeutic Uses

ClinicalTrials.gov processed this record on March 30, 2015