Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LY2245461 after Multiple Oral Administrations in Healthy Postmenopausal Wome

Phase 1

• Conditions: Reduce the number of hot flushes for postmenopausal women

• Registration Number: EUCTR2008-001372-75-DK
• Lead Sponsor: Chorus, a Division of Eli Lilly and Company

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2008-04-21
• Last Update Posted: 2 August 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 52

Inclusion Criteria

[1]Healthy postmenopausal (natural or surgical) women, 12 months without a menstrual period or perimenopausal women 6 months without a menstrual period and FSH >40 IU/L, age 45 to 65 years, inclusive; history of three or more hot flashes per day by self reporting and more than five hot flashes per day by objective monitoring a hot flash frequency of more than five hot flashes per day (24 hours) as indicated by Biolog hot flash event marking (EM) or the hot flash monitor by skin conductance recording (SCR)
[2]Body mass index between 20 and 32 40 kg/m2, inclusive.
[3]Blood pressure between 160-90 mmHg (systolic) and 90-50 mmHg (diastolic) and heart rate (sitting) between 50 and 100 beats per minute as determined by the investigator.
[4]Normal mammogram within one year and normal Pap smear within three years of the baseline visit.
[5]Willing to make themselves available for the duration of the study, and abide by the research unit policies, procedures and study restrictions.
[6]Agree not to use any prescription or over-the-counter medications during the study not approved by the study investigator.
[7]Have given written informed consent approved by Lilly/Chorus and the Ethical Review Board governing the site.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

[8] Thyroid disease, unless well controlled with TSH in normal range, and stable replacement dose for last 3 months.
[9]History or presence of clinically significant psychiatric, cardiovascular, peripheral vascular occlusive disease, respiratory, hepatic, renal, gastrointestinal, hematological, neurological, rheumatological, or endocrine disorders, including diabetes mellitus that would, in the investigator’s judgement, constitute a risk when taking the study medication or may significantly alter the absorption, metabolism or elimination of drugs.
[10]Clinically significant lab abnormality (i.e. fasting lipid profile, chemistry, hepatic function tests, TSH, etc) as judged by the investigator.
[11] Clinically significant abnormality during gynecological exams or trans-vaginal ultrasound, e.g., endometrial or endocervical polyps, any baseline ovarian cyst (except a simple cyst < 20 mm), an endometrial thickness greater or equal to 5 mm.
[12]Use of any prescription or over-the-counter medication, except thyroid hormone replacement, and certain medications that are applied to the skin, eyes, or nose that the investigator believes will not affect study drug absorption, metabolism or elimination. Standard multi-vitamins are allowed. Tylenol (acetaminophen, paracetamol) is also allowed.
[13]Vaginal estrogen therapy will not be allowed within 12 weeks of the baseline visit or during the study.
[14]Use of any medication that may affect hot flashes within 12 weeks of the baseline visit., including estrogen, progestin, androgen, antidepressants, anxiolytics (i.e. benzodiazepines), clonidine, gabapentin, SERMs (i.e. raloxifene, tamoxifen), and aromatase inhibitors.
[15]Evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies. Evidence of hepatitis C and/or positive hepatitis C antibody. Evidence of hepatitis B and/or positive hepatitis B surface antigen.
[16]Electrocardiogram reading considered outside the normal limits by the investigator, and relevant for interpretation or indicating cardiac disease including QTc (Bazett) interval >450 msec, aberrant, blocked or impaired propagation, and signs of ischemic heart disease.
[17]Smoke more than 10 cigarettes or equivalent in nicotine use or nicotine substitutes per day.
[18]Within 30 days of the initial dose of study drug, have received treatment with a drug that has not received regulatory approval for any indication
[19]Have previously completed or withdrawn from this study.
[20]Regular use of drugs of abuse and/or positive findings on urinary drug screening.
[21]Subjects who have an average weekly alcohol intake that exceeds 21 units per week or subjects unwilling to stop alcohol consumption for the duration of the study (1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits). Subjects must not drink any alcohol for 24 hours before the first dose of study medication and when in the unit.
[22]Cumulative blood donation of more than 500 mL within the previous 60 days prior to admission.
[23]Known allergies to LY2245461 or other components of the drug product.
[24]Failure for any reason to satisfy the investigator for adequate fitness to participate in the study.
[25]Anyone who can not read and understand the consent form and study instructions.
[26]Lilly employees or investigator site personnel directly affiliated with this study, and their immediate families. Immediate family is defined as a spouse, parent

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: •To investigate the safety and tolerability of multiple oral doses of LY2245461 in healthy postmenopausal women.;Secondary Objective: •To characterize the pharmacokinetics (PK) of LY2245461 administered as multiple doses given daily for 28 days in healthy postmenopausal women.<br>•To characterize the pharmacodynamic (PD) effects of LY224561 administered daily for 28 days in healthy postmenopausal women.<br>•To characterize the PK/PD dose and/or exposure response relationships.<br>;Primary end point(s): 1. Safety evaluations to include adverse events, vital signs, ECGs, etc. to be summarized using descriptive methodology.<br>2. Pharmacokinetic evaluations - parameters to be evaluated descriptively.<br>3. Pharmacodynamic evaluations - Hot flush frequency as measured by the Biolog or the patient diary, and the Hot Flash Related Daily Interference Scale.