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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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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

Conditions
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Growth Hormone Deficiency

Intervention / Treatment
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* Drug: Norditropin SimpleXx (growth hormone)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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growth hormone deficiency, circadian variation