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 12, 2011
Last verified: October 2011
  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 patients 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 patients will receive four weekly injections of LY2189265 with continued use of normal lisinopril therapy.

Part 2 is a cross-over study design. Patients 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: Baseline, Day 3, Day 24 ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics, Maximum concentration (Cmax) of lisinopril [ Time Frame: Baseline, Day 3, Day 24 ] [ Designated as safety issue: Yes ]
  • Mean, 24-hour heart rate (collected by ABPM - Ambulatory Blood Pressure Monitoring) in response to co-administration of LY2189265 and metoprolol [ Time Frame: Baseline, Day 4, Day 7 of metoprolol treatment period ] [ Designated as safety issue: Yes ]
  • Mean, 24-hour blood pressure (collected by ABPM) in response to co-administration of LY2189265 and metoprolol [ Time Frame: Baseline, Day 4, Day 7 of metoprolol treatment period ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Mean, 24-hour heart rate (collected by ABPM) in response to co-administration of LY2189265 and lisinopril [ Time Frame: Baseline, Day 3, Day 24 ] [ Designated as safety issue: Yes ]
  • Mean, 24-hour blood pressure (collected by ABPM) in response to co-administration of LY2189265 and lisinopril [ Time Frame: Baseline, Day 3, Day 24 ] [ 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 metoprolol treatment period ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics, Maximum concentration (Cmax) of metoprolol [ Time Frame: Day 4 and Day 7 of metoprolol treatment period ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 56
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
1.5 mg LY2189265 administered subcutaneously, weekly for 4 weeks and lisinopril administered orally daily in the morning for 25 days, dose as prescribed by patient's established course of therapy
Biological: LY2189265
administered subcutaneously
Drug: lisinopril
administered orally
Placebo Comparator: Placebo + lisinopril
placebo administered subcutaneously, weekly for 4 weeks and lisinopril administered orally daily in the morning for 25 days, dose as prescribed by patient's established course of therapy
Drug: lisinopril
administered orally
Drug: placebo
administered subcutaneously
Experimental: LY2189265/Metoprolol + LY2189265

Single 1.5 mg dose of LY2189265 administered subcutaneously on day 1 in treatment period 1 then 100 mg metoprolol administered orally, daily for seven days and a single 1.5 mg dose of LY2189265 administered subcutaneously prior to the metoprolol on day 5 in treatment period 2.

There is a washout period of at least 21 days between treatment periods.

Biological: LY2189265
administered subcutaneously
Drug: metoprolol
administered orally
Experimental: Metoprolol + LY2189265/LY2189265

100 mg metoprolol administered orally, daily for seven days and a single 1.5 mg dose of LY2189265 administered subcutaneously prior to the metoprolol on day 5 in treatment period 1 then a single 1.5 mg dose of LY2189265 administered subcutaneously on day 1 in treatment period 2.

There is a washout period of at least 21 days between treatment periods.

Biological: LY2189265
administered subcutaneously
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 subjects: 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 subjects: 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 kg/m2, 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
  • Have controlled mild to moderate hypertension (supine BP less than or equal to 140/90 mmHg 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 T2DM) that, in the investigator's opinion, will not significantly alter the disposition of the drug, will not place the subject 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 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 daily (QD) morning dosing regimen. Additional medication may be permitted as indicated Type 2 Diabetes Mellitus (T2DM) Subjects (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 an 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

  • 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 GLP-1-related compounds, including LY2189265, or any components of the formulation
  • Are persons 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 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 GE (e.g. gastric bypass surgery, pyloric stenosis) or could be aggravated by GLP-1 analogs (for example;esophageal reflux). Subjects 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 mL of blood within the month prior to screening
  • Have a nondominant arm circumference of greater than 42 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 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits)
  • Are subjects 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
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
Last Updated: October 12, 2011
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on April 16, 2014