Clinical trial NCT01250834: LY2189265 and Atorvastatin Interaction Study
Official title: Effect of LY2189265 on the Pharmacokinetics of Atorvastatin in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2010-12-01
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will assess if giving LY2189265 at the same time as atorvastatin affects how the body absorbs atorvastatin.


Eligibility criteria: Inclusion Criteria:

* Male subjects with female partners of child-bearing potential: Agree and whose partners agree to use two reliable methods of contraception from the time of the first dose until 3 months after the last dose of study drug, as determined by the investigator.
* Female subjects not of child-bearing potential (that is, are postmenopausal or permanently sterilized \[for example, tubal occlusion, hysterectomy, bilateral salpingectomy\]) will not be required to use contraception. Postmenopausal is defined as at least 1 year post cessation of menses (without an alternative medical cause) with follicle stimulating hormone (FSH) greater than or equal to 40 milliInternational Units per milliliter (mIU/mL).
* Female subjects who have undergone sterilization by tubal ligation: Agree to use a male or female condom used in conjunction with spermicidal gel, foam, cream, film or suppository from the time of screening until 3 months after the last dose of study drug. Such subjects must also test negative for pregnancy at the time of enrollment.
* Have a body mass index (BMI) between 18.5 and 30.0 kilograms per square meter (kg/m\^2), inclusive.
* 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 frequent blood sampling.
* Are reliable and willing to make themselves available for the duration of the study and are willing to follow the study restrictions

Exclusion Criteria:

* Are currently enrolled in, or discontinued within the last 90 days from a clinical trial involving an investigational drug or device or off-label use of a drug or device 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 or intolerance to atorvastatin.
* Have known allergies to glucagon-like peptide-1 (GLP-1)-related compounds including LY2189265.
* 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 or incretin mimetics 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 an abnormal blood pressure (after at least 5 minutes sitting) that, in the opinion of the investigator, increases the risks associated with participating in the study.
* Have a history or presence of pancreatitis (history of chronic pancreatitis or idiopathic acute pancreatitis) or gastrointestinal disorder, for example esophageal reflux or gall bladder disease, or any gastrointestinal disease which impacts absorption and distribution of study drugs (for example, gastric bypass surgery, pyloric stenosis, with the exception of appendectomy) or could be aggravated by GLP-1 analogs.
* Have a history or presence of thyroid disease.
* Show history or evidence of significant active neuropsychiatric disease.
* Regularly use known drugs of abuse and/or show positive findings on urinary drug screening.
* Show evidence of human immunodeficiency virus (HIV) 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 use over-the-counter medication within 7 days prior to dosing or prescription medication (with the exception of vitamin/mineral supplements and/or hormone replacement therapy) within 14 days prior to dosing.
* Use drugs that are known substrates, inducers, or inhibitors of cytochrome P450 (CYP) enzyme pathways or phosphorylated glycoprotein (P-gp) within 14 days prior to the first dose.
* Have donated blood of more than 500 mL within the month prior to screening.
* Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females), and are subjects unwilling to stop alcohol consumption from 48 hours before Admission (Day -1) until discharge from the unit for each treatment period, and to limit alcohol intake to a maximum of 2 units/day on all other days from screening through 48 hours prior to the post-study 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 subjects who, in the opinion of the investigator, are in any way unsuitable to participate in the study.
* Are women of child bearing potential

Primary outcomes:
measure: Pharmacokinetics of Atorvastatin: Maximum Plasma Concentration (Cmax)
timeFrame: Pre-dose to 56 hours post-dose
measure: Pharmacokinetics of Atorvastatin: Area Under the Curve (AUC)
timeFrame: Pre-dose to 56 hours post-dose
Secondary outcomes:
measure: Pharmacokinetics of Para-Hydroxyatorvastatin: Maximum Concentration (Cmax)
timeFrame: Pre-dose to 56 hours post-dose
measure: Pharmacokinetics of Para-Hydroxyatorvastatin: Area Under the Curve (AUC)
timeFrame: Pre-dose to 56 hours post-dose
measure: Pharmacokinetics of Ortho-Hydroxyatorvastatin: Maximum Concentration (Cmax)
timeFrame: Pre-dose to 56 hours post-dose
measure: Pharmacokinetics of Ortho-Hydroxyatorvastatin: Area Under the Curve (AUC)
timeFrame: Pre-dose to 56 hours post-dose
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: 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.
state: West Yorkshire
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: de la Pena A, Cui X, Geiser J, Loghin C. No Dose Adjustment is Recommended for Digoxin, Warfarin, Atorvastatin or a Combination Oral Contraceptive When Coadministered with Dulaglutide. Clin Pharmacokinet. 2017 Nov;56(11):1415-1427. doi: 10.1007/s40262-017-0531-7.