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

Healthy Clinical Trial

— LEILA-1  

Official title:

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06315205
• Other study ID #: ROV-LEBE-2023-01
• Secondary ID: 2023-503948-13
• Status: Recruiting
• Phase: Phase 1
• Start date: July 26, 2023
• Est. completion date: January 2025

Study information

• Verified date: November 2023
• Source: Rovi Pharmaceuticals Laboratories
• Contact: Clinical Operations Laboratorios farmacéuticos ROVI
• Phone: 00 44 913756230
• Email: departamento.medico[@]rovi.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

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
• 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
• 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

Locations

Country	Name	City	State
Czechia	Investigational Site number CZ-01	Praha

Sponsors (1)

Lead Sponsor	Collaborator
Rovi Pharmaceuticals Laboratories

Country where clinical trial is conducted

Czechia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	?z	Terminal phase elimination rate constant	Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
Primary	Cmax	Maximum observed plasma concentration after Letrozole LEBE administration	Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
Primary	Clast	Last observed plasma concentration after Letrozole LEBE administration	Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
Primary	tmax	Time to maximum observed concentration	Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
Primary	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
Primary	t1/2	Terminal elimination half life.	Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
Primary	AUC8	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
Primary	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	E1	Estrone	Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
Secondary	SE1	Sulfate estrone	Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
Secondary	E2	Estradiol	Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
Secondary	?z	Terminal phase elimination rate constant.	Following multiple oral administration of Femara (Treatment Period 1, Day 14)
Secondary	Cav	Average plasma concentration over a dosing interval.	Following multiple oral administration of Femara (Treatment Period 1, Day 14)
Secondary	Cmin, ss	Minimum observed plasma concentration at steady-state.	Following multiple oral administration of Femara (Treatment Period 1, Day 14)
Secondary	Cmax,ss	Maximum observed plasma concentration at steady-state	Following multiple oral administration of Femara (Treatment Period 1, Day 14)
Secondary	tmax	Time to maximum observed concentration.	Following multiple oral administration of Femara (Treatment Period 1, Day 14)
Secondary	t1/2	Terminal elimination half-life.	Following multiple oral administration of Femara (Treatment Period 1, Day 14)
Secondary	AUCt	Area under the concentration-time curve over a dosing interval.	Following multiple oral administration of Femara (Treatment Period 1, Day 14)