Study to Compare the Bioavailability, Safety and Tolerability of XM17 in Healthy, Down Regulated Young Women

An Open, Randomized, Two-way Cross-over Phase I Study to Compare the Bioavailability, Safety and Tolerability of Single s.c. Doses of 300 IU XM17 With 300 IU Gonal-f® in 36 Healthy, Down-regulated Young Women

Aim of this study is to demonstrate the bioequivalence of single subcutaneous doses of XM17 and Gonal-f® in a confirmatory design. Furthermore, safety and tolerability will be assessed in human healthy female subjects. Only female subjects will be included in the study to reach the objectives of the study.

Study Overview

• Status: Completed
• Conditions: Bioequivalence
• Intervention / Treatment: Drug: XM17; Drug: Gonal-f®; Drug: Zoladex®

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 39 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Having signed written informed consent
• Healthy female subjects of any racial origin
• 18-39 years at the time of screening
• Body mass index (BMI) between 18-29 kg/m2 and a body weight of ≥ 50 kg
• Use of oral contraceptives for contraceptive purposes only and not for regularization of menstrual cycle, for at least 3 months
• Normal uterus and two functioning ovaries
• Agrees to use an adequate method of contraception during the study
• Non-smoking or moderate smokers of < 10 cigarettes a day

Exclusion Criteria:

• Pregnancy
• Polycystic ovary syndrome, impaired ovarian function, severe endometriosis class III or IV, submucosal myoma uteri
• History of endocrine abnormalities with treatment within the last six months.
• Contraindications for the use of gonadotropins and goserelin
• Breast-feeding or being within a period of 2 months after delivery or abortion.
• Use of an injectable hormonal contraceptive within a period of 6 months prior to screening
• Treatment in the previous three months with any drug known to have a well-defined potential for toxicity to a major organ

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: XM17; XM17 will be administered by 1 mL syringes in graduated steps of 0.01 mL.	Drug: XM17; 300 IU corresponds to an injection volume of 0.5 mL.
Experimental: Gonal-f®; Gonal-f® will be provided in pens with integrated vials of 0.5 mL	Drug: Gonal-f®; 300 IU corresponds to an injection volume of 0.5 mL.; Other Names: follitropin alfa
Active Comparator: Zoladex®; Zoladex® 3.6 mg will be administered by subcutaneous injection	Drug: Zoladex®; 3.6 mg; Other Names: goserelin acetate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of single dose pharmacokinetics (Cmax)	XM17 and Gonal-f® tested statistically for bioequivalence.	Pre-dose at -10 min, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Comparison of single dose pharmacokinetics (AUC0-t)	XM17 and Gonal-f® tested statistically for bioequivalence.	Pre-dose at -10 min, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics AUC0-∞	Area under the XM17 / Gonal-f® concentration time curve from time 0 extrapolated to infinity	Pre-dose at -10 min, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Pharmacokinetics AUC0-168h	Area under the XM17 / Gonal-f® concentration time curve from time 0 to 168 h	Pre-dose at -10 min, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Pharmacokinetics Cmax,obs	Maximum XM17 / Gonal-f® concentration determined during the interval of sample taking	Pre-dose at -10 min, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Pharmacokinetics Tmax	Time to maximum XM17 / Gonal-f® concentration	Pre-dose at -10 min, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Pharmacokinetics λZ	Apparent terminal elimination rate constant.	Pre-dose at -10 min, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Pharmacokinetics t1/2	Apparent terminal elimination half life.	Pre-dose at -10 min, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Pharmacokinetics CL/F	Serum clearance after dosing	Pre-dose at -10 min, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Pharmacokinetics Vz/F	Volume of Distribution during the terminal phase after extravascular administration	Pre-dose at -10 min, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Percentage of participants with adverse events		Signing of informed consent to final data collection (27 days)

Collaborators and Investigators

• Sponsor: Merckle GmbH

Publications and helpful links

General Publications

• Lammerich A, Mueller A, Bias P. Phase I, two-way, crossover study to demonstrate bioequivalence and to compare safety and tolerability of single-dose XM17 vs Gonal-f(R) in healthy women after follicle-stimulating hormone downregulation. Reprod Biol Endocrinol. 2015 Dec 1;13:130. doi: 10.1186/s12958-015-0124-y.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: October 28, 2015
• First Submitted That Met QC Criteria: October 28, 2015
• First Posted (Estimate): October 30, 2015

Study Record Updates

• Last Update Posted (Actual): November 9, 2021
• Last Update Submitted That Met QC Criteria: November 5, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Antineoplastic Agents, Hormonal; Goserelin
• Other Study ID Numbers: XM17-02; 2008-005756-24 (EudraCT Number)