LY2189265 and Atorvastatin Interaction Study

Effect of LY2189265 on the Pharmacokinetics of Atorvastatin in Healthy Subjects

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01250834

Enrollment

Registered

2010-12-01

Start date

2010-12-31

Completion date

2011-03-31

Last updated

2014-10-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy Volunteers

Brief summary

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

Interventions

DRUGAtorvastatin

Administered orally.

BIOLOGICALLY2189265

Administered subcutaneously.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
Pharmacokinetics of Atorvastatin: Maximum Plasma Concentration (Cmax)	Pre-dose to 56 hours post-dose	—
Pharmacokinetics of Atorvastatin: Area Under the Curve (AUC)	Pre-dose to 56 hours post-dose	This measure is based on the pharmacokinetic area under the atorvastatin plasma concentration-time curve from time 0 to infinity.

Secondary

Measure	Time frame	Description
Pharmacokinetics of Para-Hydroxyatorvastatin: Maximum Concentration (Cmax)	Pre-dose to 56 hours post-dose	—
Pharmacokinetics of Para-Hydroxyatorvastatin: Area Under the Curve (AUC)	Pre-dose to 56 hours post-dose	This measure is based on the pharmacokinetic area under the para-hydroxyatorvastatin concentration-time curve from time 0 to infinity. The outcome is not available for this metabolite since the terminal elimination phase was not determinable.
Pharmacokinetics of Ortho-Hydroxyatorvastatin: Maximum Concentration (Cmax)	Pre-dose to 56 hours post-dose	—
Pharmacokinetics of Ortho-Hydroxyatorvastatin: Area Under the Curve (AUC)	Pre-dose to 56 hours post-dose	This measure is based on the pharmacokinetic area under the ortho-hydroxyatorvastatin concentration-time curve from time 0 to infinity.

Countries

United Kingdom

Participant flow

Participants by arm

Arm	Count
LY2189265 + Atorvastatin Period 1: Participants received a single 40-milligram (mg) oral dose of atorvastatin on Day 1, followed by a 7- to 10-day washout period between Day 1 of Period 1 and Day 1 of Period 2. Period 2: Participants received a single 1.5-mg subcutaneous dose of LY2189265 on Day 1, followed by a single 40-mg oral dose of atorvastatin on Day 3.	27
Total	27

Baseline characteristics

Characteristic	LY2189265 + Atorvastatin
Age, Continuous	42.7 years STANDARD_DEVIATION 15.1
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	1 Participants
Race (NIH/OMB) Black or African American	1 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	25 Participants
Region of Enrollment United Kingdom	27 participants
Sex: Female, Male Female	12 Participants
Sex: Female, Male Male	15 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	8 / 27	23 / 27	16 / 27
serious Total, serious adverse events	0 / 27	0 / 27	0 / 27

Outcome results

Primary

Pharmacokinetics of Atorvastatin: Area Under the Curve (AUC)

This measure is based on the pharmacokinetic area under the atorvastatin plasma concentration-time curve from time 0 to infinity.