r-hGH Liquid Multidose Versus Freeze-dried Multidose Bioequivalence Trial

Phase I, Open Label, Randomised Three-way Cross Over, Single-centre Trial to Assess the Bioequivalence for Two Concentrations of the New r-hGH Liquid Multidose Formulation Versus the r-hGH Freeze-dried Multidose Formulation Administered in Healthy Volunteers

The primary objective of the trial was to assess the bioequivalence for two concentrations (5.83 mg/mL and 8 mg/mL) of the new r-hGH liquid multidose formulation using the r hGH freeze-dried multidose formulation (Saizen® 8 mg, 8.8 mg/1.51 mL) as reference.

Each volunteer received three r hGH treatments, with each treatment being administered as a single subcutaneous dose of 4 mg r-hGH in a randomized sequence with at least one week of wash-out period between successive treatments.

Study Overview

• Status: Completed
• Conditions: Growth Hormone Deficiency; Growth Failure
• Intervention / Treatment: Biological: r-hGH liquid (Saizen); Biological: r-hGH liquid (Saizen); Biological: r-hGH freeze-dried

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neu-Ulm, Germany
    • AAI Pharma Deutschland GmbH & Co. KG

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Main inclusion criteria:

1. Male and female aged 18 to 45 years, inclusive; who are able to read, to write and to fully understand German language
2. Had given written Informed Consent
3. Had a body weight greater than 55 kg and a body mass index (BMI) of >20 and < or = 30 kg/m2 (BMI = weight (kg)/height (m)2)

4. Had vital signs in the following normal range:

   Ear body temperature: 35.0 - 38.0°C

   Blood pressure (BP) - after at least 3 minutes of rest, measured in the supine position:

   systolic blood pressure: 90 - 145 mmHg diastolic blood pressure : 50 - 95 mmHg Pulse rate (PR): after at least 3 minutes of rest, measured in the supine position: 40 90 bpm

5. Smoked less than 10 cigarettes per day, consented to smoke less than 5 cigarettes per day during the trial period and were able to refrain from smoking during the confinement period
6. Were able to communicate well with the Investigator and willing to comply with the requirements of the entire trial

7. Were willing to undergo pituitary down-regulation by intravenous infusion with somatostatin for 25 hours

   If female:

8. Had a negative serum pregnancy test within three weeks prior to trial start and a negative urine pregnancy test at the day before dosing
9. Were pre-menopausal and using an adequate method of non-hormonal contraception (2 barrier methods, or one barrier method with spermicide, or non-hormonal intrauterine device), sexual abstinence or females with vasectomised partners during the entire trial

Exclusion Criteria:

Main exclusion criteria:

1. Any surgical or medical condition, including findings in the medical history or in the pre trial assessments, that in the opinion of the Investigator, constituted a risk or a contraindication for the participation of the subject in the trial or that could have interfered with the trial objectives, conduct or evaluation
2. Had any clinically significant abnormal laboratory test results in the pre-trial safety laboratory tests or any clinically abnormal findings on the 12 leads resting electrocardiogram (ECG) that in the opinion of the Investigator may have increased the safety risk to the subject
3. Had positive results for drugs of abuse or alcohol test
4. Had positive results from serology examination for Hepatitis B surface antigen (HBsAg) (not due to vaccination), Hepatitis B core antibody (HBcAb) (if positive, was to be verified by test for anti-Hbc-IgM), Hepatitis C Virus (anti-HCV) and Human Immunodeficiency Virus (anti-HIV 1 and 2) at screening
5. History or presence of hypertension or other significant cardiovascular abnormalities
6. History or presence of cholelithiasis
7. Significant history or clinical evidence of auto-immune, gastrointestinal, haematological, hematopoietic, hepatic, neurological, pancreatic or renal disease
8. History or presence of diabetes
9. History or presence of tumors of the pituitary gland or hypothalamus
10. Definite or suspected personal history or family history of adverse drug reaction or hypersensitivity to drugs with a similar chemical structure to somatropin or somatostatin or its excipients, use of any chronic medication

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A	Biological: r-hGH liquid (Saizen); Treatment Arm A: r-hGH liquid multidose formulation 5.83 mg/mL, needle injection (0.686 mL); Biological: r-hGH liquid (Saizen); Treatment Arm B: r-hGH liquid multidose formulation 8.0 mg/mL, needle injection (0.5 mL)
Experimental: Arm B	Biological: r-hGH liquid (Saizen); Treatment Arm A: r-hGH liquid multidose formulation 5.83 mg/mL, needle injection (0.686 mL); Biological: r-hGH liquid (Saizen); Treatment Arm B: r-hGH liquid multidose formulation 8.0 mg/mL, needle injection (0.5 mL)
Experimental: Arm C	Biological: r-hGH freeze-dried; Treatment Arm C: r-hGH 8 mg (8.8 mg/1.51 ml) freeze-dried formulation ( reconstituted in metacresol 0.3% w/v) needle injection (0.686 mL)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Primary endpoints were the pharmacokinetic (PK) parameters of r-hGH: the area under the serum concentration-time curve from time zero to last detectable serum concentration (AUC0 t) and the maximum observed serum concentration (Cmax).	24 hours post r hGH dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Secondary endpoints included further PK parameters.	15 +/-3 days post last r hGH dose
Safety and tolerability were evaluated by adverse events (AEs), medical history, physical examination, vital signs, local tolerability, visual analog scale (VAS), ECG recordings, glycemia measurements and laboratory tests.	15 +/-3 days post last r hGH dose

Collaborators and Investigators

• Sponsor: EMD Serono
• Investigators: Principal Investigator: Michael Lissy, MD, AAIPharma Deutschland gmbH & Co. KG

Publications and helpful links

General Publications

• Liedert B, Forssmann U, Wolna P, Golob M, Kovar A. Comparison of the pharmacokinetics, safety and tolerability of two concentrations of a new liquid recombinant human growth hormone formulation versus the freeze-dried formulation. BMC Clin Pharmacol. 2010 Oct 20;10:14. doi: 10.1186/1472-6904-10-14.

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: December 16, 2009
• First Submitted That Met QC Criteria: December 16, 2009
• First Posted (Estimate): December 17, 2009

Study Record Updates

• Last Update Posted (Estimate): October 23, 2013
• Last Update Submitted That Met QC Criteria: October 22, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: Growth Hormone; bioequivalence; Saizen®; recombinant human; treatment of growth failure in children; growth hormone deficiency in adults
• Additional Relevant MeSH Terms: Failure to Thrive
• Other Study ID Numbers: 28798