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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT01034735
First received: December 16, 2009
Last updated: October 22, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Growth Failure
Growth Hormone Deficiency
Biological: r-hGH liquid (Saizen)
Biological: r-hGH freeze-dried
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: 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

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • 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). [ Time Frame: 24 hours post r hGH dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Secondary endpoints included further PK parameters. [ Time Frame: 15 +/-3 days post last r hGH dose ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 15 +/-3 days post last r hGH dose ] [ Designated as safety issue: Yes ]

Enrollment: 30
Study Start Date: July 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
Experimental: Arm B 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)

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01034735

Locations
Germany
AAI Pharma Deutschland GmbH & Co. KG
Neu-Ulm, Germany
Sponsors and Collaborators
EMD Serono
Investigators
Principal Investigator: Michael Lissy, MD AAIPharma Deutschland GmbH & Co. KG
  More Information

No publications provided by EMD Serono

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT01034735     History of Changes
Other Study ID Numbers: 28798
Study First Received: December 16, 2009
Last Updated: October 22, 2013
Health Authority: Germany: The Bavarian State Ministry of the Environment and Public Health

Keywords provided by EMD Serono:
Saizen®
bioequivalence
recombinant human
Growth Hormone
treatment of growth failure in children
growth hormone deficiency in adults

Additional relevant MeSH terms:
Endocrine System Diseases
Dwarfism, Pituitary
Failure to Thrive
Dwarfism
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Bone Diseases, Endocrine
Hypopituitarism
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on September 16, 2014