A Single Ascending Dose and Relative Bioavailability Study of LY2940680 in Healthy Subjects
| Registry | NCT01681186 |
|---|---|
| Status | Completed |
| Phase | Phase 1 |
| Study type | Interventional; randomized, crossover, masking: double, other |
| Enrollment | 30 (Actual) |
| Sponsor | Eli Lilly and Company (Industry) |
| Conditions | Healthy Participants |
| Interventions | LY2940680 Capsule(s) (Reference), LY2940680 Tablet (Test), Lansoprazole, Placebo Capsule(s) (Drug) |
| Dates | start 2012-09-01, primary completion 2012-12-01, completion 2012-12-01, first posted 2012-09-07, last updated 2019-10-21 |
| Locations | 1 site in United States |
Related Papers Related Patents Related Grants Related Experts
All trials for Healthy Participants All trials of LY2940680 Capsule(s) (Reference) All trials of LY2940680 Tablet (Test)
This study involves 2 parts, Part A and Part B. The purpose of Part A is to evaluate the safety and side effects of LY2940680 in healthy participants. Part A will involve two groups of participants, each taking up to two single doses of LY2940680 at different dose levels. There is a minimum 14 day washout period between each of the participant's doses. The purpose of Part B is to study how much of the study drug, in capsule or tablet form, gets into the bloodstream and how long the body takes to get rid of it. In addition, the effect of food and a proton pump inhibitor (PPI) on LY2940680 will be studied. Part B will involve one group of participants who will take four single doses of 100 milligrams (mg) LY2940680. There is a minimum 7 day washout period between doses. Participants may only enroll in one part. Screening is required within 28 days prior to the start of the study.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| LY2940680 (Part A) | Experimental | Drug: LY2940680 Capsule(s) (Reference) | Single escalating dose (50 mg up to 400 mg) of LY2940680 given once orally in up to 2 of 2 study periods |
| Placebo (Part A) | Placebo comparator | Drug: Placebo Capsule(s) | Placebo given once orally in up to 1 of 2 study periods |
| LY2940680 Capsule Fasted (Part B) | Experimental | Drug: LY2940680 Capsule(s) (Reference) | 100 mg LY2940680 given once orally as a capsule (reference formulation) in fasted state in 1 of 4 study periods |
| LY2940680 Tablet Fasted (Part B) | Experimental | Drug: LY2940680 Tablet (Test) | 100 mg LY2940680 given once orally as a tablet (test formulation) in fasted state in 1 of 4 study periods |
| LY2940680 Tablet Fed (Part B) | Experimental | Drug: LY2940680 Tablet (Test) | 100 mg LY2940680 given once orally as a tablet (test formulation) in fed state following a standardized, high-fat breakfast in 1 of 4 study periods |
| LY2940680 Tablet Fasted + PPI (Part B) | Experimental | Drug: LY2940680 Tablet (Test); Drug: Lansoprazole | 30 mg lansoprazole (PPI) given orally once daily for 7 days. One hour after last dose, 100 mg LY2940680 given orally once as a tablet (test formulation) in fasted state in 1 of 4 study periods |
Sex: All, ages: 18 Years to 65 Years, accepts healthy volunteers
Inclusion Criteria: * Healthy sterile males or surgically sterile females or postmenopausal females, as determined by medical history and physical examination * Body mass index of 18.5 to 32.0 kilograms per meter square (kg/m\^2) * Have clinical laboratory test results within normal reference range * Have given written informed consent approved by Lilly and the ethical review board (ERB) governing the site * Prepared to eat an entire high fat breakfast Exclusion Criteria: * Are currently enrolled in, have completed or discontinued within the last 30 days from a clinical trial involving an investigational product * Have known allergies to LY2940680, related compounds or any components of the formulation, or known allergies to lansoprazole (Part B only) * Have previously completed or withdrawn from this study or any other study investigating LY2940680, and have previously received the investigational product. Participants in Part A are not allowed to participate in Part B * Have an abnormality in the 12-lead electrocardiogram (ECG) * Have a history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data (cholecystectomy or appendectomy are allowed if surgery at least 6 months prior to screening) * 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 * Have used or intend to use over-the-counter or prescription medication within 14 days prior to dosing or during the study. Exception: participants may continue hormone replacement therapy (HRT; estrogen) * Use of herbal supplements, grapefruit juice, grapefruits, Seville orange juice, Seville oranges, or Starfruit within 7 days prior to dosing or during the study
| Milestone | Part A, Cohort 1, Sequence 1 | Part A, Cohort 1, Sequence 2 | Part A, Cohort 1, Sequence 3 | Part A, Cohort 2, Sequence 4 | Part A, Cohort 2, Sequence 5 | Part A, Cohort 2, Sequence 6 | Part B, Cohort 3, Sequence 1 | Part B, Cohort 3, Sequence 2 |
|---|---|---|---|---|---|---|---|---|
| Started | 4 | 2 | 2 | 3 | 3 | 2 | 7 | 7 |
| Completed | 4 | 2 | 2 | 3 | 3 | 2 | 7 | 7 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Arm | Deaths | Serious adverse events | Other adverse events |
|---|---|---|---|
| Placebo Capsule (Fasted) | 0 | 0/9 (0.0%) | 2/9 (22.2%) |
| 50-mg LY2940680 Capsule (Fasted) | 0 | 0/6 (0.0%) | 3/6 (50.0%) |
| 100-mg LY2940680 Capsule (Fasted) Part A or Part B | 0 | 0/20 (0.0%) | 10/20 (50.0%) |
| 100 mg LY2940680 Tablet (Fasted) | 0 | 0/14 (0.0%) | 5/14 (35.7%) |
| 100-mg LY2940680 Tablet Plus 30-mg Lansoprazole (Fasted) | 0 | 0/11 (0.0%) | 3/11 (27.3%) |
| 100-mg LY2940680 Tablet (Fed) | 0 | 0/12 (0.0%) | 5/12 (41.7%) |
| 200-mg LY2940680 Capsule (Fasted) | 0 | 0/6 (0.0%) | 3/6 (50.0%) |
| 400-mg LY2940680 Capsule (Fasted) | 0 | 0/5 (0.0%) | 3/5 (60.0%) |
| Term | Organ system | Placebo Capsule (Fasted) | 50-mg LY2940680 Capsule (Fasted) | 100-mg LY2940680 Capsule (Fasted) Part A or Part B | 100 mg LY2940680 Tablet (Fasted) | 100-mg LY2940680 Tablet Plus 30-mg Lansoprazole (Fasted) | 100-mg LY2940680 Tablet (Fed) | 200-mg LY2940680 Capsule (Fasted) | 400-mg LY2940680 Capsule (Fasted) |
|---|---|---|---|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | 0/9 | 0/6 | 1/20 | 0/14 | 0/11 | 0/12 | 0/6 | 0/5 |
| Constipation | Gastrointestinal disorders | 0/9 | 0/6 | 1/20 | 0/14 | 0/11 | 0/12 | 0/6 | 0/5 |
| Diarrhoea | Gastrointestinal disorders | 0/9 | 0/6 | 1/20 | 1/14 | 0/11 | 1/12 | 0/6 | 0/5 |
| Dry mouth | Gastrointestinal disorders | 0/9 | 0/6 | 1/20 | 0/14 | 0/11 | 0/12 | 0/6 | 0/5 |
| Eructation | Gastrointestinal disorders | 0/9 | 0/6 | 1/20 | 0/14 | 0/11 | 0/12 | 0/6 | 0/5 |
| Nausea | Gastrointestinal disorders | 1/9 | 1/6 | 2/20 | 0/14 | 0/11 | 1/12 | 2/6 | 0/5 |
| Vomiting | Gastrointestinal disorders | 0/9 | 0/6 | 2/20 | 0/14 | 1/11 | 1/12 | 0/6 | 0/5 |
| Facial pain | General disorders | 0/9 | 0/6 | 0/20 | 0/14 | 1/11 | 0/12 | 0/6 | 0/5 |
| Fatigue | General disorders | 0/9 | 0/6 | 0/20 | 0/14 | 0/11 | 1/12 | 0/6 | 0/5 |
| Feeling cold | General disorders | 0/9 | 0/6 | 1/20 | 0/14 | 0/11 | 0/12 | 0/6 | 0/5 |
| Pain | General disorders | 0/9 | 0/6 | 0/20 | 0/14 | 1/11 | 0/12 | 0/6 | 0/5 |
| Seasonal allergy | Immune system disorders | 0/9 | 0/6 | 0/20 | 0/14 | 1/11 | 0/12 | 0/6 | 0/5 |
| Tooth infection | Infections and infestations | 0/9 | 0/6 | 0/20 | 1/14 | 0/11 | 0/12 | 0/6 | 0/5 |
| Excoriation | Injury, poisoning and procedural complications | 0/9 | 0/6 | 0/20 | 0/14 | 0/11 | 1/12 | 0/6 | 0/5 |
| Muscle spasms | Musculoskeletal and connective tissue disorders | 0/9 | 0/6 | 0/20 | 0/14 | 0/11 | 0/12 | 0/6 | 2/5 |
| Neck mass | Musculoskeletal and connective tissue disorders | 0/9 | 0/6 | 0/20 | 0/14 | 1/11 | 0/12 | 0/6 | 0/5 |
| Dizziness | Nervous system disorders | 0/9 | 0/6 | 3/20 | 0/14 | 0/11 | 0/12 | 0/6 | 0/5 |
| Headache | Nervous system disorders | 2/9 | 1/6 | 6/20 | 3/14 | 0/11 | 3/12 | 3/6 | 1/5 |
| Paraesthesia | Nervous system disorders | 0/9 | 0/6 | 0/20 | 0/14 | 0/11 | 0/12 | 1/6 | 0/5 |
| Somnolence | Nervous system disorders | 0/9 | 0/6 | 1/20 | 1/14 | 0/11 | 0/12 | 0/6 | 0/5 |
| Vulvovaginal pruritus | Reproductive system and breast disorders | 0/8 | 0/6 | 1/19 | 0/14 | 0/11 | 0/12 | 0/6 | 0/3 |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | 0/9 | 1/6 | 1/20 | 0/14 | 0/11 | 0/12 | 0/6 | 1/5 |
| Throat irritation | Respiratory, thoracic and mediastinal disorders | 0/9 | 0/6 | 1/20 | 0/14 | 0/11 | 0/12 | 0/6 | 0/5 |
| Dry skin | Skin and subcutaneous tissue disorders | 0/9 | 0/6 | 0/20 | 1/14 | 0/11 | 0/12 | 0/6 | 0/5 |
| Pruritus | Skin and subcutaneous tissue disorders | 0/9 | 0/6 | 1/20 | 0/14 | 0/11 | 0/12 | 0/6 | 0/5 |
| Rash | Skin and subcutaneous tissue disorders | 0/9 | 0/6 | 1/20 | 0/14 | 0/11 | 0/12 | 0/6 | 0/5 |
| Flushing | Vascular disorders | 0/9 | 1/6 | 0/20 | 0/14 | 0/11 | 0/12 | 0/6 | 0/5 |
| Facility | City | Country | Status |
|---|---|---|---|
| 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 |