Clinical trial NCT02459418: Comparative Pharmacokinetics of AFOLIA and US Gonal-f® RFF Redi-ject After Single Subcutaneous Application
Official title: Comparative Pharmacokinetics of AFOLIA and US Gonal-f® RFF Redi-ject After Single Subcutaneous Application. A Randomised, Open Label, 2-way Cross-over Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Afolia
Follitropin
Lead sponsor: Fertility Biotech AG
Sponsor class: INDUSTRY
First posted: 2015-06-02
Enrollment: 42
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: Comparative PK study after single SC application of Afolia and the reference product (US Gonal-f®). Objective: To demonstrate equivalence within 80%-125% margin of the reference product for the area under the curve (AUC) of Afolia.

Detailed description: To demonstrate equivalence within the 80% to 125% margin of the reference product for the baseline corrected area under the follicle-stimulating hormone (FSH) serum concentration-time curve from time zero to the last quantifiable concentration of AFOLIA compared to the reference product (United States \[US\] Gonal-f® RFF)

Eligibility criteria: Inclusion Criteria:

1. Healthy female volunteers aged 18 to 42 years (inclusive) with a Body mass index of 18.0 to 32.0 kg/m2 (inclusive)
2. Subjects who have used oral contraceptives for at least 3 months before study entry and are prepared to stop taking oral contraception from screening and to use effective non-hormonal methods of birth control until completion of 1 menstrual cycle after the last dose administration
3. Women of child bearing potential must agree to use effective non-hormonal contraception for birth control until completion of 1 menstrual cycle after the last dose administration
4. Subjects with a regular menstruation cycle (25 to 34 days) before initiation of oral contraception
5. Subjects with both ovaries
6. Subjects who are negative for drugs of abuse and alcohol tests at screening and each admission
7. Subjects who are healthy as determined by pre study medical history, physical examination and 12-Lead electrocardiogram (ECG)
8. Subjects whose clinical laboratory test results are not clinically relevant and are acceptable to the investigator
9. Subjects who are able and willing to give written informed consent

Exclusion Criteria:

1. Subjects who do not conform to the above inclusion criteria
2. Subjects with polycystic ovary syndrome
3. Subjects with developing follicles or solid ovarian cysts \>2 cm or complex cysts regardless of size
4. Subjects with a history of hypersensitivity to FSH (Ovary Hyperstimulation Syndrome)
5. Subjects with impaired thyroid function (treated or untreated)
6. Subjects with a history of malignant disease
7. Subjects with aspartate aminotransferase and/or alanine aminotransferase \>2 x upper limit of normal reference range
8. Subjects with other clinically relevant findings (ECG, blood pressure, physical, laboratory examination)
9. Subjects with a smoking history of more than 5 cigarettes per day
10. Subjects with evidence of abuse of drugs or alcoholic beverages
11. Subjects with a positive screen for hepatitis B surface antigen, antibodies to the hepatitis C virus or antibodies to the human immunodeficiency virus 1/2
12. Subjects who have participated in a clinical trial within the 3 months prior to this study
13. Subjects who are unlikely to co-operate with the requirements of the study
14. Subjects with symptoms of a clinically relevant illness during the 3 weeks prior to study day -1
15. Subjects who are pregnant, lactating or attempting to become pregnant
16. Subjects with any medical condition (including a known predisposition to porphyria) that, in the opinion of the investigator, could interfere with safety of the subject or interfere with the objectives of the study
17. Subjects who are vegans or have medical dietary restrictions
18. Subjects who cannot communicate reliably with the investigator

Primary outcomes:
measure: Baseline Corrected FSH Area Under the Serum Concentration-time Curve From Zero to the Last Quantifiable Measurement [AUC(0-last)]
timeFrame: From 0 (predose),0.5, 1, 3, 6, 9, 12, 16, 20, 21, 22, 23, 24, 25, 26, 27, 28, 48, 72, 96, 120, 144, 168 and 192 hours postdose.
measure: Baseline Corrected FSH Maximum Serum Concentration (Cmax)
timeFrame: From 0 hours (predose) to 192 hours postdose.
Secondary outcomes:
measure: Baseline Corrected FSH Area Under the Serum Concentration-time Curve Extrapolated to Infinity [AUC(0-∞)]
timeFrame: From 0 hours (predose) to 192 hours postdose.
measure: Baseline Corrected Time to Reach Maximum FSH Serum Concentration (Tmax)
timeFrame: From 0 hours (predose) to 192 hours postdose.
measure: Baseline Corrected FSH Apparent Terminal Half-life
timeFrame: From 0 hours (predose) to 192 hours postdose.
measure: Baseline Corrected 17ß-Estrodiol (E2) Serum Exposure AUC(0-last)
timeFrame: From 0 hours (predose) to 192 hours postdose.
measure: Baseline Corrected E2 Cmax
timeFrame: From 0 hours (predose) to 192 hours postdose.
measure: Baseline Corrected E2 Tmax
timeFrame: From 0 hours (predose) to 192 hours postdose.
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Quintiles Drug Research Unit at Guy's Hospital
Study officials:
affiliation: Fertility Biotech AG
name: Julian Jenkins, DM FRCOG
role: STUDY_DIRECTOR
References: