Comparative Pharmacokinetics of AFOLIA and US Gonal-f® RFF Redi-ject After Single Subcutaneous Application

NCT02459418 | Completed Phase 1 Results

• 1 other identifier: FIN1002
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Keywords

Afolia; Follitropin

Outcome Measures

Primary Outcomes (2)

• Baseline Corrected FSH Area Under the Serum Concentration-time Curve From Zero to the Last Quantifiable Measurement [AUC(0-last)]

  AUC(0-last) was estimated for baseline corrected FSH in serum by noncompartmental methods using actual elapsed time from dosing. Baseline corrected concentrations were determined by subtracting the baseline concentration (collected immediately prior to dosing in that period) from the postdose concentration. Geometric mean baseline corrected FSH exposure results are presented for all subjects who received active study drug and had at least 1 measured and valid concentration at a scheduled PK time point after administration of AFOLIA or Gonal-f® RFF.

  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.

• Baseline Corrected FSH Maximum Serum Concentration (Cmax)

  Cmax was estimated for baseline corrected FSH in serum by noncompartmental methods using actual elapsed time from dosing. Baseline corrected concentrations were determined by subtracting the baseline concentration (collected immediately prior to dosing in that period) from the postdose concentration. Geometric mean baseline corrected FSH exposure results are presented for all subjects who received active study drug and had at least 1 measured and valid concentration at a scheduled PK time point after administration of AFOLIA or Gonal-f® RFF.

  From 0 hours (predose) to 192 hours postdose.

Secondary Outcomes (6)

• Baseline Corrected FSH Area Under the Serum Concentration-time Curve Extrapolated to Infinity [AUC(0-∞)]

  From 0 hours (predose) to 192 hours postdose.

• Baseline Corrected Time to Reach Maximum FSH Serum Concentration (Tmax)

  From 0 hours (predose) to 192 hours postdose.

• Baseline Corrected FSH Apparent Terminal Half-life

  From 0 hours (predose) to 192 hours postdose.

• Baseline Corrected 17ß-Estrodiol (E2) Serum Exposure AUC(0-last)

  From 0 hours (predose) to 192 hours postdose.

• Baseline Corrected E2 Cmax

  From 0 hours (predose) to 192 hours postdose.

Study Arms (2)

Afolia - US Gonal-f® (Sequence A) Arm

EXPERIMENTAL

During the Cross-Over Pharmacokinetic Phase, subjects will be randomly assigned to receive treatment sequence: (Sequence A): Single subcutaneous injection of 225IU Afolia on study day 1, followed by a single subcutaneous injection of 225IU US Gonal-f® on study day 27.

Drug: Afolia; Drug: US Gonal-f®

US Gonal-f® - Afolia (Sequence B) Arm:

ACTIVE COMPARATOR

During the Cross-Over Pharmacokinetic Phase, patients will be randomly assigned to receive treatment sequence (Sequence B): Single subcutaneous injection of 225IU US Gonal-f® on study day 1, followed by a single subcutaneous injection of 225IU Afolia on study day 27

Drug: Afolia; Drug: US Gonal-f®

Interventions

Afolia DRUG

During the Cross-Over Pharmacokinetic Phase, subjects will be randomly assigned to receive one of the following treatment sequences: Sequence A: Single subcutaneous injection of 225IU Afolia on study day 1, followed by a single subcutaneous injection of 225IU US Gonal-f® on study day 27. Sequence B: Single subcutaneous injection of 225IU US Gonal-f® on study day 1, followed by a single subcutaneous injection of 225IU Afolia on study day 27

Also known as: Follitropin Alfa

Afolia - US Gonal-f® (Sequence A) Arm; US Gonal-f® - Afolia (Sequence B) Arm:

US Gonal-f® DRUG

During the Cross-Over Pharmacokinetic Phase, subjects will be randomly assigned to receive one of the following treatment sequences: Sequence A: Single subcutaneous injection of 225IU Afolia on study day 1, followed by a single subcutaneous injection of 225IU US Gonal-f® on study day 27. Sequence B: Single subcutaneous injection of 225IU US Gonal-f® on study day 1, followed by a single subcutaneous injection of 225IU Afolia on study day 27

Also known as: Follitropin Alfa

Afolia - US Gonal-f® (Sequence A) Arm; US Gonal-f® - Afolia (Sequence B) Arm:

Eligibility Criteria

• Age: 18 Years - 42 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy female volunteers aged 18 to 42 years (inclusive) with a Body mass index of 18.0 to 32.0 kg/m2 (inclusive)
• 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
• 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
• Subjects with a regular menstruation cycle (25 to 34 days) before initiation of oral contraception
• Subjects with both ovaries
• Subjects who are negative for drugs of abuse and alcohol tests at screening and each admission
• Subjects who are healthy as determined by pre study medical history, physical examination and 12-Lead electrocardiogram (ECG)
• Subjects whose clinical laboratory test results are not clinically relevant and are acceptable to the investigator
• Subjects who are able and willing to give written informed consent

You may not qualify if:

• Subjects with polycystic ovary syndrome
• Subjects with developing follicles or solid ovarian cysts \>2 cm or complex cysts regardless of size
• Subjects with a history of hypersensitivity to FSH (Ovary Hyperstimulation Syndrome)
• Subjects with impaired thyroid function (treated or untreated)
• Subjects with a history of malignant disease
• Subjects with aspartate aminotransferase and/or alanine aminotransferase \>2 x upper limit of normal reference range
• Subjects with other clinically relevant findings (ECG, blood pressure, physical, laboratory examination)
• Subjects with a smoking history of more than 5 cigarettes per day
• Subjects with evidence of abuse of drugs or alcoholic beverages
• 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
• Subjects who have participated in a clinical trial within the 3 months prior to this study
• Subjects who are unlikely to co-operate with the requirements of the study
• Subjects with symptoms of a clinically relevant illness during the 3 weeks prior to study day -1
• Subjects who are pregnant, lactating or attempting to become pregnant
• 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

Sponsors & Collaborators

• Fertility Biotech AG: lead

Study Sites (1)

Quintiles Drug Research Unit at Guy's Hospital

London, SE1 1YR, United Kingdom

Location

MeSH Terms

Interventions

follitropin alfa

Limitations and Caveats

None reported

Results Point of Contact

• Title: Executive VP of Regulatory Affairs
• Organization: Fertility Biotech AG

maria.vazquez@fertilitybiotech.com

Study Officials

• Julian Jenkins, DM FRCOG

  Fertility Biotech AG

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2015
• First Posted: June 2, 2015
• Study Start: May 7, 2015
• Primary Completion: May 19, 2016
• Study Completion: May 19, 2016
• Last Updated: June 29, 2018
• Results First Posted: May 29, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)