A Phase I, Open Label, Dose Escalation Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Single Intramuscular Injections of Letrozole ISM® at Different Strengths in Voluntary Healthy Post Menopausal Women (LISA-1)

Rovi Pharmaceuticals Laboratories1 site in 1 country53 target enrollmentNovember 6, 2017

ConditionsHealthy

InterventionsLetrozole ISM

Overview

Phase: Phase 1
Intervention: Letrozole ISM
Conditions: Healthy
Sponsor: Rovi Pharmaceuticals Laboratories
Enrollment: 53
Locations: 1
Primary Endpoint: AUC∞
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase I, open label, dose escalation study designed to evaluate the pharmacokinetics, safety, and tolerability of single intramuscular injections of Letrozole ISM® at different strengths in voluntary healthy post menopausal women

Detailed Description

The objective of this study is to assess the pharmacokinetic profile of a single ascending doses of Letrozole ISM® (Rovi), and secondly, to evaluate safety and tolerability of single ascending doses of Letrozole ISM, measure estrogen levels, and characterize oral letrozole pharmacokinetic profile to be used in subsequent comparison to Letrozole ISM. The study will be carried out in healthy post-menopausal women who satisfy inclusion and exclusion criteria. The study consists of 3 treatment periods (TP) (TP1, TP2 and TP3) preceding by 2 Screening Periods (one for TP1 and one for TP3). In TP1, each subject will sequentially receive 1 dose daily of oral Femara (EU sourced) over a period of 14 days followed by a single intramuscular (IM) dose of Letrozole ISM (after a washout period) in TP2. Ascending doses of Letrozole ISM will be given sequentially to four Cohorts (1, 2, 3, and 4) \[NOTE: Cohorts 3 and 4 were not finally performed because the Safety Review Committee considered it was not necessary for the achieving the objectives of the study\] . All subjects who will finalize TP2 and fulfil the eligibility criteria will be offered to participate in TP3. The purpose is to have, at least, a minimum of 12 subjects receiving one oral daily dose of Femara (US sourced) 2.5 mg QD for a period of 14 days, to provide a complete pharmacokinetic (PK)/pharmacodynamic (PD) face-to-face comparison.

Registry

clinicaltrials.gov

Start Date

November 6, 2017

End Date

May 17, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Sequential

Sex

Female

Investigators

Sponsor

Rovi Pharmaceuticals Laboratories

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Healthy post-menopausal women, ≥ 18 and ≤ 75 years of age, who have achieved complete menopause, either natural or surgical, and amenorrhea, and have not been on hormone replacement therapy in the last 3 months.
•Post-menopausal subjects should have absence of menses for 1 year, and oophorectomized subjects should have absence of menses for at least 6 weeks. For oophorectomized subjects and subjects who have had a hysterectomy, a surgical pathology report documenting the absence of malignant disease is required. In addition, for oophorectomized subjects an operative report documenting bilateral oophorectomy is required.
•Baseline follicle-stimulating hormone (FSH) and 17β-estradiol plasma levels should be consistent with the post-menopausal status of the subject (FSH ≥ 40 mIU/mL; 17β-estradiol ≤ 31 pg/mL), confirmed at least 48 hours prior to dosing.
•Weight of ≥ 50 kg and a BMI ≥ 19 and ≤ 39 kg/m
•Subjects will be in good health, as determined by medical history, physical examination, vital signs assessments (pulse rate, systolic and diastolic blood pressure, and temperature), clinical laboratory evaluations, and 12-lead ECG. Minor deviations outside the reference ranges will be acceptable, if deemed not clinically significant by the investigator.
•Subjects who have not had a mammogram within the last 12 months (documentation required) must be willing to have one performed.
•Subjects with an intact uterus and cervix who have not had a Papanicolaou (pap) smear test within the last 6 months (documentation required) must be willing to have one performed.
•Subjects will have given their written informed consent to participate in the study and to abide by the study restrictions.
•Subjects should be able to communicate with clinic staff.

Exclusion Criteria

•Subjects who have a history of allergy or hypersensitivity to letrozole or any of the inactive ingredients in the last 3 months.
•Subjects who have a history of galactose intolerance, severe hereditary lactase deficiency glucose-galactose malabsorption.
•Subjects who have used estrogen or progesterone hormone replacement therapy, thyroid replacement therapy, oral contraceptives, androgens, luteinizing hormone (LH) releasing hormone analogs, prolactin inhibitors, or antiandrogens within 3 months prior to Screening.
•Subjects who have regularly taken foods or food supplements that contain high levels of Isoflavinoids, including soybean, soymilk, soynuts, chickpeas, alfalfa, fava beans, kudzu, miso and tofu in the 14 days prior to dosing (Treatment Period 1).
•The investigator and medical monitor will determine on a case-by-case basis if a subject who intakes food or food supplements containing Isoflavinoids is eligible to participate in the study.
•Subjects who have used:
•Any medications including St. John's wort, known to be potent or moderate inducers of CYP P450 3A4 in the 3 weeks prior to dosing (Treatment Period 1).
•Any medications or products known to be potent or moderate inhibitors of CYP P450 3A4 (e.g. grapefruit juice) in the 7 days prior to dosing on Treatment Period
•Any prescribed preparations within 14 days prior to dosing (Treatment Period 1), unless in the opinion of the investigator (or designee) the medication will not interfere with the study procedures or compromise safety.
•Any non-prescribed systemic or topical medications within 7 days of dosing (Treatment Period 1) unless in the opinion of the investigator (or designee) the medication will not interfere with the study procedures or compromise safety. Vitamins and minerals including the use of calcium and/or vitamin D for osteoporosis prevention are allowed.

Arms & Interventions

Cohort 1: Letrozole ISM 50 mg

14 oral doses of 2.5 mg Femara (once daily) + single IM injection of 50 mg Letrozole ISM

Intervention: Letrozole ISM

Cohort 2: Letrozole ISM 100 mg

14 oral doses of 2.5 mg Femara (once daily) + single IM injection of 100 mg Letrozole ISM

Intervention: Letrozole ISM

Cohort 3: Letrozole ISM 200 mg

14 oral doses of 2.5 mg Femara (once daily) + single IM injection of 200 mg Letrozole ISM

Intervention: Letrozole ISM

Cohort 4: Letrozole ISM 400 mg

14 oral doses of 2.5 mg Femara (once daily) + single IM injection of 400 mg Letrozole ISM

Intervention: Letrozole ISM