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

NCT01034735 | Completed Phase 1

• 1 other identifier: 28798
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Growth Failure; Growth Hormone Deficiency

Keywords

Saizen®; bioequivalence; recombinant human; Growth Hormone; treatment of growth failure in children; growth hormone deficiency in adults

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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

Study Arms (3)

Arm A

EXPERIMENTAL

Biological: r-hGH liquid (Saizen)

Arm B

EXPERIMENTAL

Biological: r-hGH liquid (Saizen)

Arm C

EXPERIMENTAL

Biological: r-hGH freeze-dried

Interventions

r-hGH liquid (Saizen) BIOLOGICAL

Treatment Arm A: r-hGH liquid multidose formulation 5.83 mg/mL, needle injection (0.686 mL)

Arm A

r-hGH freeze-dried BIOLOGICAL

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)

Arm C

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female aged 18 to 45 years, inclusive; who are able to read, to write and to fully understand German language
• Had given written Informed Consent
• 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)
• 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
• 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
• Were able to communicate well with the Investigator and willing to comply with the requirements of the entire trial
• Were willing to undergo pituitary down-regulation by intravenous infusion with somatostatin for 25 hours
• If female:
• Had a negative serum pregnancy test within three weeks prior to trial start and a negative urine pregnancy test at the day before dosing
• 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

You may not qualify if:

• 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
• 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
• Had positive results for drugs of abuse or alcohol test
• 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
• History or presence of hypertension or other significant cardiovascular abnormalities
• History or presence of cholelithiasis
• Significant history or clinical evidence of auto-immune, gastrointestinal, haematological, hematopoietic, hepatic, neurological, pancreatic or renal disease
• History or presence of diabetes
• History or presence of tumors of the pituitary gland or hypothalamus
• 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

Sponsors & Collaborators

• EMD Serono: lead

Study Sites (1)

AAI Pharma Deutschland GmbH & Co. KG

Neu-Ulm, Germany

Location

Related Publications (1)

• 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.

  PMID: 20961422 DERIVED

MeSH Terms

Conditions

Failure to Thrive; Dwarfism, Pituitary

Interventions

Human Growth Hormone

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms; 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; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Growth Hormone; Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Michael Lissy, MD

  AAIPharma Deutschland GmbH & Co. KG

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 16, 2009
• First Posted: December 17, 2009
• Study Start: July 1, 2008
• Primary Completion: August 1, 2008
• Last Updated: October 23, 2013

Record last verified: 2013-10

Locations

DE (1)