Phase 1 · Dulaglutide

NCT01324388 trial results

Pharmacokinetic and Pharmacodynamic Effect of LY2189265 on Lisinopril in Subjects With Hypertension and Metoprolol in Healthy Subjects

Pharmacokinetics, Area Under the Concentration Curve (AUC) of Lisinopril ((nanograms*hours/milliliter)/milligram), Day -1, Day 3, Day 24 of Part 1, Day -1 (Baseline). Part 1: LY2189265 + Lisinopril: 1580; Part 1: Placebo + Lisinopril: 1740.

Participants
51
Status
completed
Completed
2011-08
Sponsor
Eli Lilly and Company

As posted on ClinicalTrials.gov (NCT01324388), updated at source Oct 8, 2014. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What NCT01324388 measured first

Pharmacokinetics, Area Under the Concentration Curve (AUC) of Lisinopril(nanograms*hours/milliliter)/milligram · Day -1, Day 3, Day 24 of Part 1 · geometric mean
MeasurePart 1: LY2189265 + Lisinopriln=23Part 1: Placebo + Lisinopriln=8
Day -1 (Baseline)1580(55)1740(26)
Day 3 (n=22, 8)1660(56)1720(28)
Day 24 (n=18, 6)1540(52)1390(38)

From the results posted on ClinicalTrials.gov (NCT01324388), updated at source Oct 8, 2014.

Pharmacokinetics, Maximum Concentration (Cmax) of Lisinopril(nanograms per milliliter) per milligram · Day -1, Day 3, Day 24 in Part 1 · geometric mean
MeasurePart 1: LY2189265 + Lisinopriln=23Part 1: Placebo + Lisinopriln=8
Day -1 (Baseline)122(56)138(22)
Day 3 (n=22, 8)114(55)138(25)
Day 24 (n=18, 6)115(49)110(39)

From the results posted on ClinicalTrials.gov (NCT01324388), updated at source Oct 8, 2014.

Mean, 24-hour Heart Rate (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Metoprololbeats per minute (bpm) · Day -1, Day 4, Day 7 of Treatment 2 in Part 2 · mean
MeasurePart 2: LY2189265 + Metoprolol (Treatment 2)n=19
Day -1 (Baseline)63.7(9.6)
Day 4 (n=18)55.8(9.4)
Day 769.4(9.0)

From the results posted on ClinicalTrials.gov (NCT01324388), updated at source Oct 8, 2014.

Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Metoprololmillimeter of mercury (mm Hg) · Day -1, Day 4, Day 7 of Treatment 2 in Part 2 · mean
MeasurePart 2: LY2189265 + Metoprolol (Treatment 2)n=19
Systolic, Day -1 (Baseline)123.0(11.4)
Systolic, Day 4 (n=18)115.4(11.7)
Systolic, Day 7116.2(10.4)
Diastolic, Day -1 (Baseline)72.8(7.3)
Diastolic, Day 4 (n=18)67.2(7.5)
Diastolic, Day 771.8(6.4)

From the results posted on ClinicalTrials.gov (NCT01324388), updated at source Oct 8, 2014.

Side effects by arm

Side effects in NCT01324388

Percent of participants affected. The most common events the registry lists.

EventPart 1: LY2189265 + LisinoprilPart 1: Placebo + LisinoprilPart 2: LY2189265Part 2: MetoprololPart 2: LY2189265 + Metoprolol
Any serious event0%0%0%0%0%
Decreased appetite26.1%0%31.6%0%36.8%
Nausea21.7%0%26.3%0%26.3%
Dyspepsia21.7%0%5.3%0%0%
Abdominal pain17.4%0%5.3%5%0%
Headache13%0%0%0%5.3%
Flatulence0%12.5%0%0%5.3%
Viral infection0%12.5%0%0%0%
Procedural site reaction0%12.5%0%0%0%
Vomiting8.7%0%10.5%0%10.5%
Fatigue0%0%0%0%10.5%
Dizziness0%0%5.3%5%10.5%
Diarrhoea4.3%0%0%10%5.3%
Abdominal distension0%0%0%0%5.3%
Retching0%0%0%0%5.3%
Asthenia0%0%5.3%0%0%
Catheter site haematoma0%0%0%0%5.3%
Upper respiratory tract infection4.3%0%0%0%5.3%
Procedural pain0%0%5.3%0%0%
Alanine aminotransferase increased0%0%0%0%5.3%
Aspartate aminotransferase increased0%0%0%0%5.3%
Dehydration0%0%0%0%5.3%
Parosmia0%0%0%0%5.3%
Cough0%0%5.3%0%5.3%
Nasal congestion0%0%0%0%5.3%
Skin lesion0%0%0%0%5.3%

From the results posted on ClinicalTrials.gov (NCT01324388), updated at source Oct 8, 2014.

Secondary outcomes

What else it measured

Mean, 24-hour Heart Rate (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinoprilbeats per minute (bpm) · Day -1, Day 3, Day 24 of Part 1 · mean
MeasurePart 1: LY2189265 + Lisinopriln=22Part 1: Placebo + Lisinopriln=6
Day -1 (Baseline)69.8(8.9)68.9(6.6)
Day 3 (n=21, 6)78.3(7.9)69.3(9.0)
Day 24 (n=18, 6)77.1(9.0)71.6(13.5)

From the results posted on ClinicalTrials.gov (NCT01324388), updated at source Oct 8, 2014.

Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinoprilmillimeter of mercury (mm Hg) · Day -1, Day 3, Day 24 of Part 1 · mean
MeasurePart 1: LY2189265 + Lisinopriln=22Part 1: Placebo + Lisinopriln=6
Systolic, Day -1 (Baseline)129.4(14.1)130.1(14.9)
Systolic, Day 3 (n=21, 6)125.3(11.5)127.1(13.4)
Systolic, Day 24 (n=18, 6)121.1(10.3)123.8(16.2)
Diastolic, Day -1 (Baseline)76.9(8.6)74.1(7.7)
Diastolic, Day 3 (n=21, 6)77.1(8.3)72.6(5.1)
Diastolic, Day 24 (n=18, 6)73.8(9.4)71.2(7.8)

From the results posted on ClinicalTrials.gov (NCT01324388), updated at source Oct 8, 2014.

Pharmacokinetics, Area Under the Concentration Curve (AUC) of Metoprolol When Administered With LY2189265nanograms*hour per milliliter (ng*h/mL) · Day 4 and Day 7 of Treatment 2 in Part 2 · geometric mean
MeasurePart 2: LY2189265 + Metoprolol Crossovern=20
Day 4617(69)
Day 7 (n=17)813(63)

From the results posted on ClinicalTrials.gov (NCT01324388), updated at source Oct 8, 2014.

Pharmacokinetics, Maximum Concentration (Cmax) of Metoprolol When Administered With LY2189265nanograms per milliliter (ng/mL) · Day 4 and Day 7 of Treatment 2 in Part 2 · geometric mean
MeasurePart 2: LY2189265 + Metoprolol Crossovern=20
Day 435.7(63)
Day 7 (n=19)47.2(66)

From the results posted on ClinicalTrials.gov (NCT01324388), updated at source Oct 8, 2014.

The trial

How NCT01324388 was run

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.

  • 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.
  • 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.
  • 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).
  • 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).
Who could join the trial

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...

Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.

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