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

Overview[ - collapse ][ - ]

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.
ConditionDiabetes Mellitus, Type 2
InterventionBiological: LY2189265
Drug: metoprolol
Drug: lisinopril
Drug: placebo
PhasePhase 1
SponsorEli Lilly and Company
Responsible PartyEli Lilly and Company
ClinicalTrials.gov IdentifierNCT01324388
First ReceivedMarch 25, 2011
Last UpdatedOctober 12, 2011
Last verifiedOctober 2011

Tracking Information[ + expand ][ + ]

First Received DateMarch 25, 2011
Last Updated DateOctober 12, 2011
Start DateMarch 2011
Estimated Primary Completion DateAugust 2011
Current 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]
Current 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]

Descriptive Information[ + expand ][ + ]

Brief TitleA Study of the Effect of LY2189265 on Two Blood Pressure Drugs
Official TitlePharmacokinetic and Pharmacodynamic Effect of LY2189265 on Lisinopril in Subjects With Hypertension and Metoprolol in Healthy Subjects
Brief Summary
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.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 1
Study DesignAllocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment
ConditionDiabetes Mellitus, Type 2
InterventionBiological: LY2189265
administered subcutaneously
Drug: metoprolol
administered orally
Drug: lisinopril
administered orally
Drug: placebo
administered subcutaneously
Study Arm (s)
  • 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
  • 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
  • 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.
  • 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.

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment56
Estimated Completion DateAugust 2011
Estimated Primary Completion DateAugust 2011
Eligibility 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
GenderBoth
Ages18 Years
Accepts Healthy VolunteersAccepts Healthy Volunteers
ContactsNot Provided
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT01324388
Other Study ID Numbers11552
Has Data Monitoring CommitteeNo
Information Provided ByEli Lilly and Company
Study SponsorEli Lilly and Company
CollaboratorsNot Provided
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
Verification DateOctober 2011

Locations[ + expand ][ + ]

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
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
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