Evaluation of the Pharmacokinetics, Safety, and Tolerability of IM Letrozole LEBE in Healthy Post-menopausal Women (LEILA-1)

A Phase I, Open Label, Dose Escalation Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Single Intramuscular Injections of Letrozole LEBE at Different Strengths in Voluntary Healthy Post-Menopausal Women.

This is a Phase I, open label, sequential, single ascending dose (SAD) study to evaluate the pharmacokinetic (PK), safety, and tolerability of Letrozole LEBE in healthy post-menopausal women.

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy
• Intervention / Treatment: Drug: Letrozole LEBE 75 mg; Drug: Letrozole LEBE 150 mg; Drug: Letrozole LEBE 225 mg

Detailed Description

The study consists of 1 Screening Period and 2 treatment periods. Evaluation of eligibility and allocation of subject number to the volunteers will be performed after Screening. It is planned that subjects will be enrolled in three groups of approximately 30 subjects in each group (Groups 1 to 3), in order to ensure 15 completed subjects per group in Treatment Period 1 and Treatment Period 2. In Treatment Period 1, each subject will sequentially receive 1 dose daily of oral Femara (2.5 mg) over a period of 14 days followed by a single intramuscular (IM) dose of Letrozole LEBE (after a washout period) in Treatment Period 2. Ascending doses of Letrozole LEBE will be given to Groups 1, 2 and 3. Safety and tolerability will be assessed in all groups by the incidence and severity of Adverse Events (AEs) and Serious AEs (SAEs), concomitant medication use, vital sign assessments, clinical laboratory evaluations, 12 lead ECGs, physical examination, and body weight/BMI. The end of the clinical trial will be the last visit of the last subject at Day 197 of Treatment Period 2 or any additionally required 4-weeks safety follow up visits, when plasma levels of letrozole are detectable, whichever occurs later. Those remaining subjects with detectable plasma levels of letrozole could be followed every 4 weeks.

The sample size was estimated based on a minimum number necessary to obtain a preliminary assessment regarding the drug's PK and safety profile over the planned dose range. No formal sample size calculation was made for this study.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 1

Contacts and Locations

Study Locations

• Czechia
  • Prague, Czechia
    • Investigational Site number CZ-01

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy post-menopausal women.
• Capable of providing informed consent.
• Weight of ≥50 kg and a BMI ≥19 and ≤39 kg/m2.
• 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.
• 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 prior to Screening.
• Subjects who have used: any medications including St. John's wort or any medications or products known to be potent or moderate inhibitors of CYP P450 3A4.
• Subjects who have been diagnosed with osteoporosis.
• Subjects who have an abnormality at Screening or prior to first dose that in the opinion of the investigator increases the risk of participating in the study.
• Subjects who have any clinically significant abnormal physical examination or laboratory safety findings at screening.
• Subjects who have relevant diseases or clinically significant abnormal relevant findings at Screening, as determined by medical history, physical examination, laboratory, ECG, DEXA, and breast and pelvic examination.
• Subjects who have history of any significant chronic disease.
• History of cancer within the past 5 years with the exception of non-melanoma skin cancer.
• Subjects who have a history of drug-dependence, and recent history of alcoholism or abuse of alcohol.
• Subjects who have received a drug in research or have participated in other clinical trials within 90 days, prior to dosing.
• Any other unspecified reason that, in the opinion of the investigator (or designee) or sponsor, makes the subject unsuitable for enrolment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Letrozol LEBE 75 mg	Drug: Letrozole LEBE 75 mg; 14 oral doses of Femara 2.5 mg/daily + 28-days (at least) washout period + single IM injection of Letrozole LEBE 75 mg
Experimental: Cohort 2: Letrozol LEBE 150 mg	Drug: Letrozole LEBE 150 mg; 14 oral doses of Femara 2.5 mg/daily + 28-days (at least) washout period + single IM injection of Letrozole LEBE 150 mg
Experimental: Cohort 3: Letrozol LEBE 225 mg	Drug: Letrozole LEBE 225 mg; 14 oral doses of Femara 2.5 mg/daily + 28-days (at least) washout period + single IM injection of Letrozole LEBE 225mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
λz	Terminal phase elimination rate constant	Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
Cmax	Maximum observed plasma concentration after Letrozole LEBE administration	Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
Clast	Last observed plasma concentration after Letrozole LEBE administration	Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
tmax	Time to maximum observed concentration	Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
tlag	Lag time before observation of quantifiable concentrations in plasma.	Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
t1/2	Terminal elimination half life.	Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
AUC∞	Area under the concentration time curve from time zero extrapolated to infinity.	Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
AUClast	Area under the concentration time curve from time zero up to the last quantifiable concentration.	Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
E1	Estrone	Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
SE1	Sulfate estrone	Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
E2	Estradiol	Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
λz	Terminal phase elimination rate constant.	Following multiple oral administration of Femara (Treatment Period 1, Day 14)
Cav	Average plasma concentration over a dosing interval.	Following multiple oral administration of Femara (Treatment Period 1, Day 14)
Cmin, ss	Minimum observed plasma concentration at steady-state.	Following multiple oral administration of Femara (Treatment Period 1, Day 14)
Cmax,ss	Maximum observed plasma concentration at steady-state	Following multiple oral administration of Femara (Treatment Period 1, Day 14)
tmax	Time to maximum observed concentration.	Following multiple oral administration of Femara (Treatment Period 1, Day 14)
t1/2	Terminal elimination half-life.	Following multiple oral administration of Femara (Treatment Period 1, Day 14)
AUCτ	Area under the concentration-time curve over a dosing interval.	Following multiple oral administration of Femara (Treatment Period 1, Day 14)

Collaborators and Investigators

• Sponsor: Rovi Pharmaceuticals Laboratories

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2023
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: March 11, 2024
• First Submitted That Met QC Criteria: March 11, 2024
• First Posted (Actual): March 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Breast cancer; Intramuscular; Letrozol LEBE
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Estrogen Antagonists; Aromatase Inhibitors; Letrozole
• Other Study ID Numbers: ROV-LEBE-2023-01; 2023-503948-13 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No