Diurnal Variation of Exogenous Peptides (GH Puls/Jurgita I)

Pharmacokinetic Profiles of GH Using Two Different Administration Regimes; a Bolus and an Infusion Both With and Without Exercise, in Adults With Growth Hormone Deficiency

This is an exploratory trial with four cross-over arms measuring the pharmacokinetic and pharmacodynamic profiles of growth hormone using two different modes of growth hormone administration (subcutaneous infusion into the abdomen or subcutaneous bolus injection in the thigh) in 8 adult male or female patients with growth hormone deficiency during interval exercise or in supine rest. The order of dosing regimen within the groups and between the groups will be randomised. All patients will go through four different treatment sessions:A/B Single subcutaneous bolus injection, supine rest without/with interval exercise, sessions C/D: Continuous subcutaneous infusion, supine rest without/with interval exercise. Hypotheses: 1) There is day-to-day variation of exogenous growth hormone, 2)Concentration of growth hormone decreases due to exercise compared to supine rest, 3)There is a circadian variation in pharmacokinetics of exogenous growth hormone infused subcutaneously

Study Overview

• Status: Completed
• Conditions: Growth Hormone Deficiency
• Intervention / Treatment: Drug: Norditropin SimpleXx (growth hormone)

Detailed Description

The subjects will attend a screening visit and four treatment sessions. The dosing visits will comprise either 2-day hospital stay for the bolus injection group or 3 day hospital stay for the infusion group.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Aarhus C, Denmark, 8000
    • Aarhus University Hospital
  • Central Denmark Region
    • Aarhus C, Central Denmark Region, Denmark, 8000
      • Medical Department M, Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• AGHD male or female subjects
• Stable GH replacement therapy for at least 3 months
• Body Mass Index 18,5 to 35.0 kg/m2
• Achieved final height
• Age ≥ 18 years

Exclusion Criteria:

• Known or suspected allergy to trial product or components of the trial product
• Subjects with active malignancy
• Severe cardiac insufficiency classified according to NYHA III-IV
• Unstable angina pectoris, acute myocardial infarction within the last 12 months
• Severe, uncontrolled hypertension: sitting blood pressure > 180/110 mmHg
• HbA1C > 7,5 %
• Impaired kidney function: plasma creatinine ≥ 150 umol/l according to the hospital lab.
• Impaired liver function: liver parameters exceed 2 times or more the upper normal limit, according to the hospital lab.
• Patients on insulin treatment
• Stable pituitary replacement therapy for less than 3 months
• Participation in any other clinical trial involving any investigational products within the last three months prior to this trial
• Any diseases judged by the investigator that could affect the trial
• Women of fertile age, who are pregnant, planning to become pregnant or breast-feeding. Women of fertile age, who are not currently using adequate contraception methods such as: contraceptive pills, IUD or who had not undergone hysterectomy or sterilization

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Norditropin SimpleXx sc bolus injection; Single sc bolus injection of 3 mg growth hormone without interval exercise	Drug: Norditropin SimpleXx (growth hormone); 3mg/subject/day over two consecutive days; Other Names: Norditropin® SimpleXx®
Other: Norditropin SimpleXx single sc injection; Single sc bolus injection of 3 mg growth hormone with interval exercise	Drug: Norditropin SimpleXx (growth hormone); 3mg/subject/day over two consecutive days; Other Names: Norditropin® SimpleXx®
Other: Norditropin SimpleXx contin. sc infusion; Continuous sc infusion of 3 mg growth hormone without interval exercise	Drug: Norditropin SimpleXx (growth hormone); 3mg/subject/day over two consecutive days; Other Names: Norditropin® SimpleXx®
Other: Norditropin SimpleXx cont. sc infusion; Continuous sc infusion of 3 mg growth hormone with interval exercise	Drug: Norditropin SimpleXx (growth hormone); 3mg/subject/day over two consecutive days; Other Names: Norditropin® SimpleXx®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic profiles of growth hormone	Pharmacokinetic profiles of growth hormone administrated subcutaneously (3 mg/day) as a bolus in the adult patients with growth hormone deficiency during interval exercise or in supine rest.	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic profiles of growth hormone	To compare pharmacokinetic profiles of growth hormone administrated subcutaneously (3 mg/day) as an infusion in the adult patients with growth hormone deficiency during interval exercise or in supine rest.	60 hours

Collaborators and Investigators

• Sponsor: Aarhus University Hospital
• Collaborators: Novo Nordisk A/S
• Investigators: Principal Investigator: Torben Laursen, professor, Institute of Pharmacology, Aarhus University

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: March 22, 2010
• First Submitted That Met QC Criteria: March 22, 2010
• First Posted (Estimate): March 23, 2010

Study Record Updates

• Last Update Posted (Estimate): January 9, 2014
• Last Update Submitted That Met QC Criteria: January 8, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: growth hormone deficiency; circadian variation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Musculoskeletal Diseases; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Endocrine; Pituitary Diseases; Dwarfism; Bone Diseases, Developmental; Hypopituitarism; Dwarfism, Pituitary; Endocrine System Diseases; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: 2010/0121