Clinical trial NCT01706783: A Trial Investigating the Safety, Tolerability, Availability and Distribution in the Body of Once-weekly Long-acting Growth Hormone (Somapacitan) Compared to Once Daily Norditropin NordiFlex® in Adults With Growth Hormone Deficiency
Official title: A Randomised, Open-labelled, Active-controlled, Multiple Dose, Dose Escalating, Sequential Dose Group Trial Investigating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Once-weekly Long-acting Growth Hormone (NNC0195-0092, Somapacitan) Compared to Once-daily Norditropin NordiFlex® in Adults With Growth Hormone Deficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Growth Hormone Disorder
Adult Growth Hormone Deficiency
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2012-10-15
Enrollment: 35
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is conducted in Europe. The aim of the trial is to investigate the safety, tolerability, availability and distribution in the body of once-weekly long-acting growth hormone (NNC0195-0092, somapacitan) compared to once daily Norditropin NordiFlex® in adults with growth hormone deficiency (GHD).


Eligibility criteria: Inclusion Criteria:

* Adults with GHD as defined in the consensus guidelines for the diagnosis and treatment of adults with GHD
* Stable human growth hormone (hGH) replacement therapy for at least 3 months

Exclusion Criteria:

* Participation in another clinical trial within 3 months or receipt of any investigational medicinal product within 3 months prior to randomisation
* Active malignant disease or malignant disease within the last 5 years with exception of fully treated local basal cell carcinoma or carcinoma in situ of cervix
* Proliferative retinopathy judged by retina-photo within the last year - only with concomitant diabetes
* Heart insufficiency, New York Heart Association (NYHA) class above 2
* Adults with GHD with poorly controlled diabetes mellitus with a glycosylated haemoglobin (HbA1c) 64 mmol/mol (8.0%) and/or insulin treatment
* Stable pituitary replacement therapy for less than 3 months

Primary outcomes:
measure: Incidence of adverse events (AEs)
timeFrame: From first administration of trial product and up until Day 49
Secondary outcomes:
measure: NNC0195-0092 (somapacitan) only: Area under the curve, AUC (0-168h)
timeFrame: From 0 to 168 hours
measure: Norditropin NordiFlex® only: AUC (0-24h)
timeFrame: From 0 to 24 hours
measure: NNC0195-0092 (somapacitan), first dose administration only: AUC (0-168h)
timeFrame: From 0 to 168 hours
measure: Norditropin NordiFlex®, first dose administration only: AUC (0-24h)
timeFrame: From 0 to 24 hours
measure: NNC0195-0092 (somapacitan): Maximum serum concentration (Cmax)
timeFrame: From 0 to 168 hours
measure: Norditropin NordiFlex®: Cmax
timeFrame: From 0 to 24 hours
measure: Insulin-like growth factor I (IGF-I): AUC (0-168h)
timeFrame: From 0 to 168 hours
measure: IGF-I: Cmax
timeFrame: From 0 to 168 hours
measure: Insulin-like growth factor binding protein-3 (IGFBP-3): AUC IGFBP-3(0-168h)
timeFrame: From 0 to 168 hours
measure: IGFBP-3: Cmax
timeFrame: From 0 to 168 hours
Other outcomes:
Locations:
city: København Ø
country: Denmark
facility: Novo Nordisk Investigational Site
city: Odense
country: Denmark
facility: Novo Nordisk Investigational Site
city: Århus C
country: Denmark
facility: Novo Nordisk Investigational Site
city: Stockholm
country: Sweden
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR,1452)
role: STUDY_DIRECTOR
References:
citation: Juul Kildemoes R, Hojby Rasmussen M, Agerso H, Overgaard RV. Optimal Monitoring of Weekly IGF-I Levels During Growth Hormone Therapy With Once-Weekly Somapacitan. J Clin Endocrinol Metab. 2021 Jan 23;106(2):567-576. doi: 10.1210/clinem/dgaa775.
citation: Papathanasiou T, Agerso H, Damholt BB, Hojby Rasmussen M, Kildemoes RJ. Population Pharmacokinetics and Pharmacodynamics of Once-Daily Growth Hormone Norditropin(R) in Children and Adults. Clin Pharmacokinet. 2021 Sep;60(9):1217-1226. doi: 10.1007/s40262-021-01011-3. Epub 2021 Apr 17.
citation: Juul RV, Rasmussen MH, Agerso H, Overgaard RV. Pharmacokinetics and Pharmacodynamics of Once-Weekly Somapacitan in Children and Adults: Supporting Dosing Rationales with a Model-Based Analysis of Three Phase I Trials. Clin Pharmacokinet. 2019 Jan;58(1):63-75. doi: 10.1007/s40262-018-0662-5.
citation: Rasmussen MH, Janukonyte J, Klose M, Marina D, Tanvig M, Nielsen LF, Hoybye C, Andersen M, Feldt-Rasmussen U, Christiansen JS. Reversible Albumin-Binding GH Possesses a Potential Once-Weekly Treatment Profile in Adult Growth Hormone Deficiency. J Clin Endocrinol Metab. 2016 Mar;101(3):988-98. doi: 10.1210/jc.2015-1991. Epub 2016 Jan 4.