A Study of LY2216684 in Healthy Participants Receiving Albuterol or Propanolol

Lilly

Status and phase: Completed; Phase 1

Conditions: Major Depressive Disorder

Treatments: Drug: propranolol; Drug: placebo for propranolol; Drug: albuterol; Drug: LY2216684; Drug: placebo for LY2216684; Drug: placebo for albuterol

Study type: Interventional

Funder types: Industry

Identifiers

NCT01263197

H9P-EW-LNCI (Other Identifier)

12598

Details and patient eligibility

About

The purpose of this study is to determine the effect of LY2216684 on heart rate of participants receiving Albuterol and Propranolol. Information about any side effects that may occur will also be collected.

Enrollment: 48 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Are overtly healthy, as determined by medical history and physical examination.
• Male participants - Agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug.
• Female participants - Are women of child-bearing potential who test negative for pregnancy at the time of enrollment, have used a reliable method of birth control for 6 weeks prior to administration of study drug, and agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug; or Women not of child-bearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause [at least 1 year without menses or 6 months without menses and a follicle stimulating hormone (FSH) >40 milli-international units per milliliter (mIU/mL)].
• Have a body weight >50 kilograms (kg).
• 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 blood sampling as per the protocol.
• Have normal blood pressure and pulse rate (sitting position) as determined by the investigator.
• Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures.
• Have given written informed consent approved by Lilly and the ethical review board (ERB) governing the site.

Exclusion criteria

• Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or off-label use of a drug or device other than the study drug, 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 LY2216684, albuterol (Group 1 only), propranolol (Group 2 only), or related compounds.
• Are persons who have previously completed or withdrawn from this study or any other study investigating LY2216684 within 6 months prior to screening.
• 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 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.
• Have a history of or current asthma, including exercise induced asthma.
• Have a history or show evidence of significant active neuropsychiatric disease or have a history of suicide attempt or ideation.
• 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.
• Are women with a positive pregnancy test or women who are lactating.
• Intend to use over-the-counter or prescription medication (including hormonal contraceptives) within 14 days prior to dosing unless deemed acceptable by the investigator and Sponsor's medical monitor
• Have donated blood of more than 500 milliliters (mL) within the last month.
• Have an average weekly alcohol intake that exceeds 14 units per week, or are unwilling to stop alcohol consumption 48 hours prior to check-in in each period and while resident at the Clinical Research Unit (CRU) [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].
• Consume 5 or more cups of coffee (or other beverages of comparable caffeine content) per day, on a habitual basis, or any participants unwilling to adhere to study caffeine restrictions.
• Have used any tobacco-containing or nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months prior to enrollment.
• Have consumed grapefruit or grapefruit-containing products 7 days prior to enrollment and during the study.
• Have a documented or suspected history of glaucoma.
• Participants determined to be unsuitable by the investigator for any reason.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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48 participants in 6 patient groups

LY2216684, albuterol, LY2216684+albuterol

Experimental group

Description:

LY2216684 as an 18 milligram (mg) oral dose on days 1-5 and placebo for albuterol on days 1, 3 and 5 in first intervention period, placebo for LY2216684 on days 1-5 and albuterol as a 2 mg oral dose on days 1, 3 and 5 in the second intervention period, and LY2216684 as an 18 mg oral dose on days 1-5 and albuterol as a 2 mg oral dose on days 1, 3 and 5 in the third intervention period. There is a minimum 7 day washout between each intervention period.

Treatment:

Drug: LY2216684

Drug: albuterol

Drug: placebo for LY2216684

Drug: placebo for albuterol

albuterol, LY2216684+albuterol, LY2216684

Experimental group

Description:

Placebo for LY2216684 on days 1-5 and albuterol as a 2 mg oral dose on days 1, 3 and 5 in the first intervention period, LY2216684 as an 18 mg oral dose on days 1-5 and albuterol as a 2 mg oral dose on days 1, 3 and 5 in the second intervention period, and LY2216684 as an 18 mg oral dose on days 1-5 and placebo for albuterol on days 1, 3 and 5 in third intervention period. There is a minimum 7 day washout between each intervention period.

Treatment:

Drug: LY2216684

Drug: albuterol

Drug: placebo for LY2216684

Drug: placebo for albuterol

LY2216684+albuterol, LY2216684, albuterol

Experimental group

Description:

LY2216684 as an 18 mg oral dose on days 1-5 and albuterol as a 2 mg oral dose on days 1, 3 and 5 in the first intervention period, LY2216684 as an 18 mg oral dose on days 1-5 and placebo for albuterol on days 1, 3 and 5 in second intervention period, Placebo for LY2216684 on days 1-5 and albuterol as a 2 mg oral dose on days 1, 3 and 5 in the third intervention period. There is a minimum 7 day washout between each intervention period.

Treatment:

Drug: LY2216684

Drug: albuterol

Drug: placebo for LY2216684

Drug: placebo for albuterol

LY2216684, propranolol, LY2216684+propranolol

Experimental group

Description:

LY2216684 as an 18 mg oral dose on days 1-5 and placebo for propranolol on days 1, 3 and 5 in first intervention period, placebo for LY2216684 on days 1-5 and propranolol as a 40 mg oral dose on days 1, 3 and 5 in the second intervention period, and LY2216684 as an 18 mg oral dose on days 1-5 and propranolol as a 40 mg oral dose on days 1, 3 and 5 in the third intervention period. There is a minimum 7 day washout between each intervention period.

Treatment:

Drug: propranolol

Drug: placebo for propranolol

Drug: LY2216684

Drug: placebo for LY2216684

propranolol, LY2216684+propranolol, LY2216684

Experimental group

Description:

Placebo for LY2216684 on days 1-5 and propranolol as a 40 mg oral dose on days 1, 3 and 5 in the first intervention period, LY2216684 as an 18 mg oral dose on days 1-5 and propranolol as a 40 mg oral dose on days 1, 3 and 5 in the second intervention period, and LY2216684 as an 18 mg oral dose on days 1-5 and placebo for propranolol on days 1, 3 and 5 in third intervention period. There is a minimum 7 day washout between each intervention period.

Treatment:

Drug: propranolol

Drug: placebo for propranolol

Drug: LY2216684

Drug: placebo for LY2216684

LY2216684+propranolol, LY2216684, propranolol

Experimental group

Description:

LY2216684 as an 18 mg oral dose on days 1-5 and propranolol as a 40 mg oral dose on days 1, 3 and 5 in the first intervention period, LY2216684 as an 18 mg oral dose on days 1-5 and placebo for propranolol on days 1, 3 and 5 in second intervention period, placebo for LY2216684 on days 1-5 and propranolol as a 40 mg oral dose on days 1, 3 and 5 in the third intervention period. There is a minimum 7 day washout between each intervention period.

Treatment:

Drug: propranolol

Drug: placebo for propranolol

Drug: LY2216684

Drug: placebo for LY2216684