Evaluation of IM Letrozole ISM® Pharmacokinetics, Safety, and Tolerability in Healthy Post-menopausal Women (LISA-1)

What this trial studies

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

Conditions in scope

• Healthy

Interventions

• Letrozole ISM (Drug) — 2.5 mg Femara + single IM injection of 50-400 mg Letrozole ISM

Who can join

Women only · Ages 18 Years to 75 Years · Accepts healthy volunteers.

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/m2.
• 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.

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 1.

Eligibility wording paraphrased from the public record. View the full criteria on ClinicalTrials.gov before contacting a site.

Where it’s happening

Status & timeline

• Overall status: Completed
• Study type: Interventional
• Phase: PHASE1
• Start date: 2017-11-06
• Primary completion: 2024-05-17
• Last update posted: 2024-12-04
• First posted: 2018-01-17

Sponsor & contact

Lead sponsor: Rovi Pharmaceuticals Laboratories (Industry)

For trial site contact information, use the official record at ClinicalTrials.gov. Contact details change frequently and the public record is the source of truth.

Outcome measures

Primary outcomes

• λz (Following single intramuscular administration of Letrozole ISM (Period 2, Day 1))
  Terminal phase elimination rate constant
• Cmax (Following single intramuscular administration of Letrozole ISM (Period 2, Day 1))
  Maximum observed plasma concentration
• Cmax/D (Following single intramuscular administration of Letrozole ISM (Period 2, Day 1))
  Dose-normalized Maximum observed plasma concentration
• tmax (Following single intramuscular administration of Letrozole ISM (Period 2, Day 1))
  Time to maximum observed concentration
• tlag (Following single intramuscular administration of Letrozole ISM (Period 2, Day 1))
  Lag time before observation of quantifiable concentrations in plasma

Related ClearedRx care

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