Effective growth hormone replacement with once-weekly somapacitan in Japanese children with growth hormone deficiency: Results from REAL4, a phase 3 clinical trial.

Objective: Somapacitan is a long-acting growth hormone (GH) derivative developed for the treatment of GH deficiency (GHD). This study evaluates the efficacy and tolerability of somapacitan in Japanese children with GHD after 104 weeks of treatment and after switch from daily GH.

Design: Subanalysis on Japanese patients from a randomised, open-labelled, controlled parallel-group phase 3 trial (REAL4, NCT03811535).

Effective GH Replacement With Somapacitan in Children With GHD: REAL4 2-year Results and After Switch From Daily GH.

Context: Somapacitan is a long-acting GH derivative for treatment of GH deficiency (GHD).

Objective: Evaluate the efficacy and tolerability of somapacitan in children with GHD after 2 years of treatment and after the switch from daily GH.

Design: A randomized, multinational, open-labelled, controlled parallel group phase 3 trial, comprising a 52-week main phase and 3-year safety extension (NCT03811535).

Weekly somapacitan had no adverse effects on glucose metabolism in adults with growth hormone deficiency.

Purpose: The long-term effects of long-acting growth hormone (LAGH) analogues on glucose metabolism in adult growth hormone deficiency (AGHD) are not known. We investigated the impact of LAGH somapacitan, administered once-weekly, on glucose metabolism in patients with AGHD.

Methods: In post hoc-defined analyses, we compared the effects of somapacitan with daily growth hormone (GH) and placebo on fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β) in patients with AGHD across a unique data set from three phase 3 randomized controlled trials (REAL 1, REAL 2 and REAL Japan).

Psychometric Validation of the Growth Hormone Deficiency-Child Treatment Burden Measure (GHD-CTB) and the Growth Hormone Deficiency-Parent Treatment Burden Measure (GHD-PTB).

Purpose: The aim was to evaluate the measurement properties of the Growth Hormone Deficiency-Child Treatment Burden Measure-Child (GHD-CTB-Child), a patient-reported outcome (PRO) for children aged 9 to < 13 years; the Growth Hormone Deficiency-Child Treatment Burden Measure-Observer (GHD-CTB-Observer), an observer-reported outcome (ObsRO) version completed by parents/guardians of children with growth hormone deficiency (GHD) aged 4 to < 9 years; and the Growth Hormone Deficiency-Parent Treatment Burden Measure (GHD-PTB), a PRO that assesses the treatment burden of parents/guardians living with children with GHD aged 4 to < 13 years.

Methods: A non-interventional, multi-center, clinic-based study across 30 private practice and large institutional sites in the United States and the United Kingdom was conducted. The sample consisted of 145 pre-pubertal children aged 9 to < 13 years at enrollment with a physician confirmed GHD diagnosis as well as 98 parents/guardians of pre-pubertal younger children aged 4 to < 9 years at enrollment with a physician confirmed GHD diagnosis.

Weekly Somapacitan is Effective and Well Tolerated in Children With GH Deficiency: The Randomized Phase 3 REAL4 Trial.

Context: Somapacitan, a once-weekly reversible albumin-binding GH derivative, is evaluated in children with GH deficiency (GHD).

Objective: To demonstrate efficacy and safety of somapacitan vs daily GH.

Methods: REAL4 is a randomised, multinational, open-labeled, active-controlled parallel group phase 3 trial, comprising a 52-week main trial and 3-year extension (NCT03811535).

Dose-exposure-IGF-I response of once-weekly somapacitan in adults with GH deficiency.

Objective: Growth hormone (GH) replacement therapy in patients with adult growth hormone deficiency (AGHD) is individually titrated due to variable dose-responses among patients. The aim of this study was to provide clinical guidance on dosing and titration of the novel long-acting GH derivative somapacitan based on analyses of somapacitan dose-insulin-like growth factor I (IGF-I) responses in AGHD patients.

Design: Analyses of dosing information, 4364 somapacitan concentration samples and 4880 IGF-I samples from 330 AGHD patients treated with somapacitan in three phase 3 trials.

Absorption, metabolism and excretion of once-weekly somapacitan, a long-acting growth hormone derivative, after single subcutaneous dosing in human subjects.

Somapacitan is a reversible albumin-binding growth hormone (GH) derivative in clinical development for once-weekly administration in patients with adult GH deficiency (AGHD) and children with GH deficiency (GHD). To date, the use of somapacitan in AGHD or severe AGHD has been approved in the USA and Japan, respectively. This study (ClinicalTrials.

Assessing the Impact of Growth Hormone Deficiency (GHD) in Adults: Interpreting Change of the Treatment-Related Impact Measure-Adult Growth Hormone Deficiency (TRIM-AGHD).

Background: This study's purpose was to assess the minimal important difference (MID) for the Treatment-Related Impact Measure-Adult Growth Hormone Deficiency (TRIM-AGHD), a patient-reported outcome measure assessing growth hormone deficiency (GHD) impacts. The measure was demonstrated to have adequate psychometric measurement properties, and be reliable and valid. For scores to be interpretable, the TRIM-AGHD must be responsive to treatment benefit and the MID in scores quantified.

Pharmacokinetics and Pharmacodynamics of Once-Weekly Somapacitan in Children and Adults: Supporting Dosing Rationales with a Model-Based Analysis of Three Phase I Trials.

Background: Somapacitan, a long-acting growth hormone (GH) derivative, has been well-tolerated in children with GH deficiency (GHD) and adults (healthy and adult GHD), in phase I, single- and multiple-dose trials, respectively, and has pharmacokinetic and pharmacodynamic properties supporting a once-weekly dosing regimen.

Objective: In the absence of a multiple-dose phase I trial in children with GHD, the aim was to develop a pharmacokinetic/pharmacodynamic model to predict somapacitan exposure and insulin-like growth factor-I (IGF-I) response after once-weekly multiple doses in both children and adults with GHD.

Methods: Pharmacokinetic/pharmacodynamic models were developed from pharmacokinetic and IGF-I profiles in three phase I trials of somapacitan (doses: healthy adults, 0.

Safety and convenience of once-weekly somapacitan in adult GH deficiency: a 26-week randomized, controlled trial.

Objective: Somapacitan is a reversible albumin-binding growth hormone (GH) derivative, developed for once-weekly administration. This study aimed to evaluate the safety of once-weekly somapacitan vs once-daily Norditropin. Local tolerability and treatment satisfaction were also assessed.

Somapacitan, a once-weekly reversible albumin-binding GH derivative, in children with GH deficiency: A randomized dose-escalation trial.

Objective: To evaluate the safety, local tolerability, pharmacodynamics and pharmacokinetics of escalating single doses of once-weekly somapacitan, a reversible, albumin-binding GH derivative, vs once-daily GH in children with GH deficiency (GHD).

Design: Phase 1, randomized, open-label, active-controlled, dose-escalation trial (NCT01973244).

Patients: Thirty-two prepubertal GH-treated children with GHD were sequentially randomized 3:1 within each of four cohorts to a single dose of somapacitan (0.

Understanding Treatment Burden for Children Treated for Growth Hormone Deficiency.

Objective: Growth hormone deficiency (GHD) treatment for children requires growth hormone injections, typically administered daily until the child reaches adult height. Child GHD treatment burden is not well understood and no disease-specific measures exist to assess this burden. The purpose of the study was to explore GHD treatment burden for children and their parents by conducting concept elicitation interviews supporting a theoretical model of the impact of GHD treatment.

Understanding burden of illness for child growth hormone deficiency.

Purpose: Research demonstrates that children and adolescents with growth hormone deficiency (GHD) are impacted in multiple ways beyond their short stature; however, there are no disease-specific measures to assess these impacts. The purpose of this study was to examine the burden of GHD on children and adolescents, and to conduct concept elicitation to develop a model of the impact of GHD to support a disease-specific outcome measure.

Methods: Four focus groups and 52 telephone interviews were conducted with children with GHD and parents/guardians of children with GHD to understand the experience and impacts from the child's perspective, reported by children or parent-observers about the impact on the child.

Reversible Albumin-Binding GH Possesses a Potential Once-Weekly Treatment Profile in Adult Growth Hormone Deficiency.

Context: NNC0195-0092 is a reversible, albumin-binding GH derivative, developed for once-weekly administration.

Objectives: The objective of the study was to evaluate safety, local tolerability, pharmacodynamics, and pharmacokinetics of multiple, once-weekly doses of NNC0195-0092, compared with daily GH.

Design And Setting: This was a phase 1, randomized, open-label, active-controlled, multiple-dose, dose-escalation trial.

Impact of adult growth hormone deficiency on daily functioning and well-being.

Background: Adult Growth Hormone Deficiency (AGHD) is a debilitating condition resulting from tumors, pituitary surgery, radiation of the head, head injury, or hypothalamic-pituitary disease. This qualitative study was conducted to better understand the multi-faceted impacts and treatment effects of GHD on adult patients' daily lives.Seven focus groups and four telephone interviews were conducted in three countries.

A reversible albumin-binding growth hormone derivative is well tolerated and possesses a potential once-weekly treatment profile.

Context: Human growth hormone (hGH) replacement therapy currently requires daily sc injections for years/lifetime, which may be both inconvenient and distressing for patients. NNC0195-0092 is a novel hGH derivative intended for once-weekly treatment of GH deficiency. A noncovalent albumin binding moiety is attached to the hGH backbone.

Assessing the impact of growth hormone deficiency and treatment in adults: development of a new disease-specific measure.

Context: Approximately 50 000 adults in the United States are diagnosed with GH deficiency, which has negative impacts on cognitive functioning, psychological well-being, and quality of life.

Objective: This paper presents development and validation of a patient-reported outcome measure (PRO), the Treatment-Related Impact Measure-Adult Growth Hormone Deficiency (TRIM-AGHD). The TRIM-AGHD was developed to measure the impact of GH deficiency and its treatment.

Biochemical markers of bone turnover in tibia fracture patients randomly assigned to growth hormone (GH) or placebo injections: Implications for detection of GH abuse.

Context: It has been argued that increased levels of bone remodelling markers are not suitable indicators of GH abuse, as bone injuries per se increase the expression levels of these markers.

Objective: To investigate the impact of a recovering tibia fracture on circulating bone markers in subjects receiving placebo or GH treatment.

Design And Setting: A randomised, double-blind, placebo-controlled trial of up to 16weeks GH treatment, followed by a 16-week washout.

Normal sweat secretion despite impaired growth hormone-insulin-like growth factor-I axis in obese subjects.

Adults with GH deficiency are known to exhibit reduced sweating. Whether sweating capacity is impacted in obese subjects with impaired GH secretion have not previously been investigated. The main objective was to investigate sweat secretion rate and the GH-IGF-I axis in obese subjects before and after weight loss.

Long-acting pegylated human GH in children with GH deficiency: a single-dose, dose-escalation trial investigating safety, tolerability, pharmacokinetics and pharmacodynamics.

Objective: GH replacement therapy currently requires daily injections, which may be inconvenient and distressing for young patients. This study determined the safety, tolerability, pharmacokinetics and pharmacodynamics of escalating single doses of a pegylated GH (NNC126-0083) developed for once-weekly administration, in children with GH deficiency (GHD).

Design And Methods: Thirty children (age ≥6 and ≤12 years, weight ≥16 kg) were randomised to NNC126-0083 or daily GH treatment.

Pegylated long-acting human growth hormone possesses a promising once-weekly treatment profile, and multiple dosing is well tolerated in adult patients with growth hormone deficiency.

Background: Recombinant human GH (rhGH) replacement therapy in children and adults currently requires daily sc injections for several years or lifelong, which may be both inconvenient and distressing for patients. NNC126-0083 is a pegylated rhGH developed for once-weekly administration.

Objectives: Our objective was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of NNC126-0083 in adult patients with GH deficiency (GHD).

Multiple doses of pegylated long-acting growth hormone are well tolerated in healthy male volunteers and possess a potential once-weekly treatment profile.

Objectives: Recombinant human growth hormone (rhGH) replacement therapy in children and adults currently requires daily subcutaneous injections for several years or lifelong. The current study examined safety, tolerability, pharmacokinetic and pharmacodynamic response parameters after single and multiple doses of a long-acting rhGH preparation (NNC126-0083).

Design: Randomized, double-blinded, placebo-controlled, multiple-dose, dose-escalating (0·02, 0·04, 0·08 and 0·16 mg protein/kg), sequential dose group trial.

Pegylated long-acting human growth hormone is well-tolerated in healthy subjects and possesses a potential once-weekly pharmacokinetic and pharmacodynamic treatment profile.

Background: Recombinant human GH (rhGH) is usually administered as a daily sc injection, which may be both inconvenient and distressing for patients. NNC126-0083 is a pegylated rhGH developed with the aim of reducing serum clearance and thereby prolonging the exposure leading to once-weekly sc administration.

Objectives: In this first human dose trial, the safety, tolerability, pharmacokinetics, and pharmacodynamic parameters of a single administration of NNC126-0083 were evaluated.

Growth hormone stimulates the collagen synthesis in human tendon and skeletal muscle without affecting myofibrillar protein synthesis.

In skeletal muscle and tendon the extracellular matrix confers important tensile properties and is crucially important for tissue regeneration after injury. Musculoskeletal tissue adaptation is influenced by mechanical loading, which modulates the availability of growth factors, including growth hormone (GH) and insulin-like growth factor-I (IGF-I), which may be of key importance. To test the hypothesis that GH promotes matrix collagen synthesis in musculotendinous tissue, we investigated the effects of 14 day administration of 33-50 microg kg(-1) day(-1) recombinant human GH (rhGH) in healthy young individuals.