Multiple Dose FSH-GEX(TM) in Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
The aim of the current study is the pharmacokinetic and pharmacodynamic characterization of a multiple dose administration of FSH-GEX™ in healthy pituitary-suppressed female volunteers, in comparison with two marketed comparator products or placebo.

Detailed Description
-----------------
Healthy pituitary-suppressed female subjects received multiple doses of FSH-GEX at one of 2 different dose levels (75 IU and 150 IU dosing once daily (QD), or 150 IU (dosing once every other day (QAD)) for maximal 7 Days. They were compared with subjects who received a urinary FSH or a recombinant FSH or placebo.

Official Title
-----------------
A Phase I, Mono-center, Placebo and Comparator Controlled, Single-blind, Randomized, Parallel Group, Clinical Study to Determine Multiple Dose Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of FSH-GEX(TM) Administered Subcutaneously in Healthy Pituitary-suppressed Female Volunteers

Conditions
-----------------
Female Infertility

Intervention / Treatment
-----------------
* Drug: FSH-GEX™
* Drug: recombinant FSH
* Drug: urinary FSH
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female subjects from 18-40 years of age at screening. Subjects must be in good health as determined by medical and gynecological history, physical and gynecological examination, vital signs, body measurements, electrocardiogram, and laboratory tests Subjects must be willing to use additional non-hormonal contraception Subjects must have used a combined oral contraceptive, combined contraceptive vaginal ring or combined contraceptive patch Vital signs which are within the following ranges: systolic blood pressure between 90-140 mmHg, diastolic blood pressure between 50-90 mmHg, pulse rate between 40 - 100 bpm Subjects must have a body weight of minimally 50.0 kg with a BMI between 18.0 and 29.9 kg/m2 Able to provide written informed consent prior to study participation. Able to communicate well with the investigator and to understand and comply with the requirements of the study. Exclusion Criteria: Smokers of more than 5 cigarettes per day. Average daily intake of more than 3 units of alcohol per day (where 1 unit equals 250 mL of beer, 125 mL of wine or 25 mL of spirits) or an average weekly intake of more than 21 units alcohol. Use of any prescription drug or over-the-counter medication from screening until the end-of-study visit, without prior approval of the investigator. Paracetamol® is acceptable without prior approval. Any drugs that may reduce the effectiveness of combination oral contraceptive (COC) from screening until the end-of-study visit Administration of any investigational product or use of any investigational device within 30 days prior to Screening. Donation or loss of 500 mL or more of blood within 90 days prior to first dosing of FSH-GEX(TM). History of acute or chronic bronchospastic disease History of allergies for drugs, seafood, nuts, eggs, wasp-stings; history of atopic allergy. A known hypersensitivity to any of the study drugs. Any surgical or medical condition which might alter the absorption, distribution, metabolism, or excretion of drugs or which may jeopardize the subject in case of participation in the study. History or presence of any malignancy. Determined or suspected pregnancy. Breast feeding women. History of (or current) endocrine abnormalities Contraindication for the use of oral contraceptives Contraindication for the use of follitropin alfa, follicle-stimulating hormone (FSH) or any of the excipients (hypersensitivity to follitropin alfa, FSH or any of the excipients; tumors of the hypothalamus or the pituitary gland; ovarian enlargement or cyst not due to polycystic ovarian disease; gynecological bleeding of unknown origin; ovarian, uterine, or mammary carcinoma). Porphyria or family history of porphyria. History of ovarian surgery. Any ovarian or abdominal abnormality that would interfere with adequate ultrasound investigation. An abnormal cervical smear History or presence of an immune-compromising disease, or a positive human immunodeficiency virus (HIV) test result in the past or at the screening visit. History of Hepatitis B or C, or a positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result at the screening visit. History of drug or alcohol abuse within the 12 months prior to the screening visit or evidence of such abuse Planned surgery or hospitalization during the period of the study. Concurrent participation or participation within 30 days before screening in another clinical trial, or participation in more than 3 clinical studies within 12 months, prior to the expected date of enrolment into the study or previous participation in the 104676-CS0160 (FSH-GEXTM) study. Injection of one or more doses of any depot contraceptive drug /drug combination ≤10 months prior to screening.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FSH-GEX 75 IU<br>follitropin epsilon 75 IU QD | Drug: FSH-GEX™<br> <br> * Other names: follitropin epsilon;|
| Experimental: FSH-GEX 150 IU<br>follitropin epsilon 150 IU QD | Drug: FSH-GEX™<br> <br> * Other names: follitropin epsilon;|
| Experimental: FSH-GEX 150 IU QAD<br>follitropin epsilon 150 IU QAD | Drug: FSH-GEX™<br> <br> * Other names: follitropin epsilon;|
| Active Comparator: recombinant FSH<br>Gonal-f 150 IU QD | Drug: recombinant FSH<br> <br> * Other names: Gonal-f;|
| Active Comparator: urinary FSH<br>Bravelle 150 IU QD | Drug: urinary FSH<br> <br> * Other names: Bravelle;|
| Placebo Comparator: Placebo<br>Placebo QD | Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety and tolerability of FSH-GEX™ following multiple dose administration by subcutaneous injection | frequency of dose related adverse events, measurement of vital signs, body measurements, transvaginal ultrasound, ECG and laboratory values in comparison to placebo and the two comparators with marketing authorization | 43 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pharmacokinetic profile of FSH-GEX™ following multiple dose administration by subcutaneous injection (part 1) | Peak Plasma Concentration (Cmax) | 28 time points up to 14 days post-dose | 
| pharmacokinetic profile of FSH-GEX™ following multiple dose administration by subcutaneous injection (part 2) | Area under the plasma concentration versus time curve (AUC) | 28 time points up to 14 days post-dose | 
| pharmacodynamic parameters of FSH-GEX™ following multiple dose administration by subcutaneous injection | Estradiol (E2), Luteinizing Hormone (LH) and inhibin B serum levels | 17 time points up to 14 days post-dose | 
| pharmacodynamic parameters of FSH-GEX™ following multiple dose administration by subcutaneous injection | follicular response and endometrial thickness as determined by transvaginal ultrasonography | 9 time points up to14 days post-dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
in-vitro fertilization, reproductive disorder