scholarly journals A Randomized Phase 2 Study of Long-Acting TransCon GH vs Daily GH in Childhood GH Deficiency

2017 ◽  
Vol 102 (5) ◽  
pp. 1673-1682 ◽  
Author(s):  
Pierre Chatelain ◽  
Oleg Malievskiy ◽  
Klaudziya Radziuk ◽  
Ganna Senatorova ◽  
Magdy O. Abdou ◽  
...  
Keyword(s):  
Adverse Events ◽  
Gh Deficiency ◽  
Area Under The Curve ◽  
Study Drug ◽  
Height Velocity ◽  
Controlled Study ◽  
Open Label ◽  
Safety And Efficacy ◽  
Treatment Naïve ◽  
Long Acting

Abstract Context: TransCon Growth Hormone (GH) (Ascendis Pharma) is a long-acting recombinant sustained-release human GH prodrug in development for children with GH deficiency (GHD). Objective: To compare the pharmacokinetics, pharmacodynamics, safety, and efficacy of weekly TransCon GH to that of daily GH in prepubertal children with GHD. Design: Randomized, open-label, active-controlled study of three doses of weekly TransCon GH versus daily Genotropin (Pfizer). Setting: Thirty-eight centers in 14 European countries and Egypt. Patients: Prepubertal male and female treatment-naïve children with GHD (n = 53). Interventions: Subjects received one of three TransCon GH doses (0.14, 0.21, or 0.30 mg GH/kg/wk) or Genotropin 0.03 mg GH/kg/d for 26 weeks. Main Outcome Measures: GH and insulinlike growth factor-1 (IGF-1) levels, growth, adverse events, and immunogenicity. Results: Both GH maximum concentration and area under the curve were similar following TransCon GH or Genotropin administration at comparable doses. A dose response was observed, with IGF-1 standard deviation scores increasing into the normal range for all three TransCon GH doses. Annualized mean height velocity for the three TransCon GH doses ranged from 11.9 cm to 13.9 cm, which was not statistically different from 11.6 cm for Genotropin. Adverse events were mild to moderate, and most were unrelated to the study drug. Injection site tolerance was good. One TransCon GH subject developed a low-titer, nonneutralizing antibody response to GH. Conclusions: The results suggest that long-acting TransCon GH is comparable to daily Genotropin for GH (pharmacokinetics) and IGF-1 (pharmacodynamics) levels, safety, and efficacy and support advancement into phase 3 development.

scholarly journals A Randomized Safety and Efficacy Study of Somavaratan (VRS-317), a Long-Acting rhGH, in Pediatric Growth Hormone Deficiency

2016 ◽  
Vol 101 (3) ◽  
pp. 1091-1097 ◽  
Author(s):  
Wayne V. Moore ◽  
Huong Jil Nguyen ◽  
Gad B. Kletter ◽  
Bradley S. Miller ◽  
Douglas Rogers ◽  
...  
Keyword(s):  
Dose Finding ◽  
Hormone Deficiency ◽  
Height Velocity ◽  
Pediatric Endocrinology ◽  
Open Label ◽  
Prepubertal Children ◽  
Safety And Efficacy ◽  
Dose Study ◽  
Dosing Regimens ◽  
Long Acting

Abstract Context: Somavaratan (VRS-317) is a long-acting form of recombinant human GH under development for children and adults with GH deficiency (GHD). Objectives: To determine the optimal somavaratan dose regimen to normalize IGF-1 in pediatric GHD and to evaluate safety and efficacy of somavaratan over 6 months. Design: Open-label, multicenter, single ascending dose study followed by 6-month randomized comparison of 3 dosing regimens. Setting: Twenty-five United States pediatric endocrinology centers. Patients: Naive-to-treatment, prepubertal children with GHD (n = 68). Intervention(s): Patients received single sc doses of somavaratan (0.8, 1.2, 1.8, 2.7, 4.0, or 6.0 mg/kg) during the 30-day dose-finding phase, then were randomized to somavaratan 1.15 mg/kg weekly, 2.5 mg/kg twice monthly, or 5.0 mg/kg monthly for 6 months. Main Outcome Measures: Safety, pharmacokinetics, pharmacodynamics, 6-month height velocity (HV). Results: Somavaratan pharmacokinetics was linearly proportional to dose; dose-dependent increases in the magnitude and duration of IGF-1 responses enabled weekly, twice-monthly or monthly dosing. A single dose of somavaratan sustained IGF-1 responses for up to 1 month. No somavaratan or IGF-1 accumulation occurred with repeat dosing. Mean annualized HVs for somavaratan administered monthly, twice monthly, or weekly (7.86 ± 2.5, 8.61 ± 2.7, and 7.58 ± 2.5 cm/y, respectively) were similar between groups. Adverse events were mostly mild and transient. Conclusions: Somavaratan demonstrated clinically meaningful improvements in HV and IGF-1 in prepubertal children with GHD, with no significant differences between monthly, twice-monthly, or weekly dosing.

scholarly journals Safety and Efficacy of Switching Injected Peptide Long-Acting Somatostatin Receptor Ligands to Once Daily Oral Paltusotine: ACROBAT Edge Phase 2 Study

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A526-A527
Author(s):  
Monica R Gadelha ◽  
Murray B Gordon ◽  
Mirjana Doknic ◽  
Emese Mezősi ◽  
Miklós Tóth ◽  
...  
Keyword(s):  
Adverse Events ◽  
Treatment Period ◽  
Somatostatin Receptor ◽  
Study Drug ◽  
Receptor Ligands ◽  
Primary Analysis ◽  
Once Daily ◽  
Safety And Efficacy ◽  
Somatostatin Receptor Ligands ◽  
Long Acting

Abstract Patients with acromegaly not cured by surgery are often initially treated with injected peptide long-acting somatostatin receptor ligands (SRLs). Non-peptide small molecules can also activate the somatostatin receptor and do so with a high degree of precision for the target therapeutic receptor subtype. Paltusotine (formerly CRN00808) is a small molecule somatostatin type 2 (SST2) receptor agonist with high oral bioavailability (70%) and pharmacokinetic profile suitable for once daily dosing. In healthy volunteers, paltusotine has been shown to lower growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels. We hypothesized that patients with acromegaly could switch from injected SRLs to once daily oral paltusotine while maintaining baseline IGF-1 levels. ACROBAT Edge (NCT03789656) was a single-arm study designed to evaluate the safety and efficacy of switching from injected SRLs to paltusotine in patients with acromegaly. The primary analysis population consisted of those who had not achieved normal IGF-1 levels despite stable therapy with long-acting octreotide or lanreotide. Eligible patients received their last injection of SRL 4 weeks prior to switching to once daily oral paltusotine monotherapy for a 13-week treatment period. The starting dose of 10 mg per day was uptitrated in 10 mg increments at specified study visits to a maximal dose of 40 mg per day based on protocol specified study drug toleration and IGF-1 criteria. The primary endpoint was change in IGF-1 from baseline to the completion of the 13-week treatment period. Statistical testing was based on non-parametric Wilcoxon Sign Rank test of whether the median change is different from zero. In addition, the rise in IGF-1 during a 4-week washout period was used to provide supportive evidence of efficacy. Twenty-five patients were enrolled in the primary analysis group, three patients discontinued from the study for non-study drug related reasons, two during the treatment period and one during the washout period after completing treatment. The primary endpoint was achieved as paltusotine treatment resulted in no significant change in IGF-1 levels at week 13 compared to baseline [change in IGF-1 =-0.034 (-0.107, 0.107), median (IQR), p>0.6]. Of the 23 patients who completed the dosing period, 20 (87%) achieved IGF-1 levels at the end of treatment that were within 20% of baseline or lower. Median IGF-1 values rose significantly after paltusotine washout (p<0.0001). The most common treatment-emergent adverse events (>10%) included: headache, arthralgia, fatigue, peripheral swelling, paresthesia and hyperhidrosis. There were no discontinuations due to adverse events and no treatment related serious adverse events. These results suggest that patients with acromegaly treated with injected SRLs can switch to oral paltusotine while maintaining IGF-1 and that paltusotine appeared to be well tolerated.

486 Timing and Duration of Adverse Events in a Clinical Trial of Lower-Sodium Oxybate in Participants With Narcolepsy With Cataplexy

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A192-A192
Author(s):  
Richard Bogan ◽  
Nancy Foldvary-Schaefer ◽  
Roman Skowronski ◽  
Abby Chen ◽  
Michael Thorpy
Keyword(s):  
Adverse Events ◽  
Study Drug ◽  
Drug Dose ◽  
Sodium Oxybate ◽  
Open Label ◽  
Double Blind ◽  
Peak Incidence ◽  
Safety Population ◽  
Titration Period ◽  
Treatment Naïve

Abstract Introduction This analysis evaluated treatment-emergent adverse events (TEAEs) during a double-blind, placebo-controlled, randomized withdrawal trial (NCT03030599) of lower-sodium oxybate (LXB; Xywav™), an FDA-approved treatment for excessive daytime sleepiness or cataplexy in narcolepsy. Methods At study entry, participants were taking sodium oxybate (SXB) alone, SXB with other anticataplectics, other anticataplectics alone, or were anticataplectic treatment-naive. Participants taking SXB transitioned to the same LXB dose (gram-for-gram); oxybate-naive participants initiated LXB (4.5 g/night). TEAEs were analyzed in the safety population (N=201, received ≥1 study drug dose) during a 12-week open-label optimized treatment/titration period (while other anticataplectics were tapered/discontinued) and subsequent 2-week stable-dose period (SDP). TEAE duration was defined as time from TEAE start to end date (or end of SDP, if TEAE end date was unrecorded). Results LXB-emergent TEAEs varied by treatment at entry. Anticataplectic treatment-naive participants reported TEAEs including headache (n=36/90, 40%; median duration [range]=1 [1–76] day), nausea (n=19/90, 21%; duration=9 [1–37] days), and dizziness (n=15/90, 17%; duration=10 [1–117] days); peak incidence was week 2 (n=8/89, 9%) for headache, week 3 (n=3/88, 3%) for dizziness, and week 1 (n=6/90, 7%) for nausea. Anticataplectic treatment-naive participants (n=13/90, 14%) also reported decreased appetite, with relatively long duration (58 [2–358] days). Participants taking SXB alone reported TEAEs including headache (n=17/52, 33%; duration=1 [1–122] day) and diarrhea (n=4/52, 8%; duration=41 [2–101] days); peak headache incidence was week 4 (n=4/52, 8%); diarrhea had no peak. Participants taking other anticataplectics alone reported TEAEs including headache (n=14/36, 39%; duration=1 [1–94] day), nausea (n=9/36, 25%; duration=3 [1–16] days), and dizziness (n=9/36, 25%; duration=4 [1–29] days); peak incidence was week 1 (n=3/36, 8%) for headache, week 6 (n=2/32, 6%) for nausea, and week 4 (n=3/33, 9%) for dizziness. One participant taking SXB with other anticataplectics (n=1/23, 4%) reported headache in weeks 1–2 and 4; one reported nausea (4%) persisting from week 1 to 8. Overall, study discontinuations attributed to TEAEs were 20/57 (35%). Conclusion Most TEAEs with LXB treatment occurred early, were consistent with the known SXB safety profile, and were relatively short-lived (except decreased appetite). Participants previously taking SXB reported fewer TEAEs than oxybate-naive participants. Support (if any) Jazz Pharmaceuticals, Inc.

scholarly journals Safety, Pharmacokinetics, and Antiviral Activity of a Novel HIV Antiviral, ABX464, in Treatment-Naive HIV-Infected Subjects in a Phase 2 Randomized, Controlled Study

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Jean-Marc Steens ◽  
Didier Scherrer ◽  
Paul Gineste ◽  
P. Noel Barrett ◽  
Supparatpino Khuanchai ◽  
...  
Keyword(s):  
Adverse Events ◽  
Safety Data ◽  
Study Drug ◽  
Primary Objective ◽  
Controlled Study ◽  
Double Blind ◽  
Antiviral Effects ◽  
Randomization Code ◽  
Treatment Naïve ◽  
Dose Ranging

ABSTRACT We investigated the safety and antiviral effects of an anti-HIV compound (ABX464) with a unique mechanism of viral replication inhibition. This was a randomized, double-blind, placebo-controlled, dose-ranging study in treatment-naive HIV-infected patients. Participants were assigned to eight groups; each group included eight subjects receiving either the study compound, ABX464 (n = 6), or the corresponding placebo (n = 2), according to a randomization code. The first dose administered was 25 mg, given once or 3 times a day over a 2- to 3-week period. Ascending doses of up to 150 mg were delivered after review of the safety data. The primary objective of the study was to assess the safety and tolerability of ABX464 after repeated oral administrations in subjects infected by HIV. Sixty-six subjects were enrolled and were randomized. Sixty-three subjects completed the study according to the study protocol. Twenty-one adverse events (AEs) were reported by 7 subjects out of 16 (44%) who received placebo, and 158 AEs were reported by 39 subjects out of 50 (78%) who received the study drug. In the ABX464 treatment group, all of these adverse events were mild to moderate. No subjects discontinued treatment due to drug-related AEs. Administration of ABX464 at up to 150 mg once a day was safe and well tolerated in HIV-infected subjects. An efficacy signal with respect to a reduction of the viral load by ABX464 was detected, mainly in subjects treated at the highest dose. Further studies will be required to demonstrate antiviral effects in HIV-infected subjects in combination with other antiretroviral therapies. (This study is registered on the ClinicalTrials.gov website under registration no. NCT02452242.)

A Randomized Placebo Controlled Phase II Trial of Prevention of Severe Oral Mucositis Using Single Dose Velafermin in Patients Receiving Myeloablative Therapy and Autologous Hematopoietic Stem Cell Transplant (AHSCT).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 615-615 ◽  
Author(s):  
Michael W. Schuster ◽  
J. Mehta ◽  
E.K. Waller ◽  
R.M. Rifkin ◽  
I. Micallef ◽  
...  
Keyword(s):  
Stem Cell ◽  
Adverse Events ◽  
Oral Mucositis ◽  
Interim Analysis ◽  
Safety Information ◽  
Study Drug ◽  
Controlled Study ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Safety And Efficacy

Abstract Oral mucositis (OM) is a commonly occurring side effect in patients (pts) undergoing AHSCT. Velafermin, recombinant human fibroblast growth factor-20, is under investigation for the prevention of severe OM. Previous studies demonstrated that velafermin at 30 mcg/kg was well tolerated and was effective in reducing the incidence of severe mucositis. The primary objective of this multicenter, randomized, double-blind, placebo controlled study was to confirm safety and efficacy of 30 mcg/kg velafermin for prevention of severe OM incidence (grade 3/4 OM based on the WHO grading system). The secondary objective was to evaluate safety and efficacy of 10 and 60 mcg/kg doses to better define the therapeutic range. Pts were randomized to receive placebo or velafermin at 30, 10 or 60 mcg/kg in a 3:3:1:1 ratio 24–36 hrs after stem cell infusion. Randomization was stratified by study center and OM risk factors identified from the previous placebo controlled study in a similar population including conditioning regimen and body mass index (BMI ≥30). Pts with multiple myeloma or lymphoma (≥18 y.o.) receiving ≥2X106 /kg CD34+ cells following chemotherapy with or without Total Body Irradiation (TBI) were eligible. OM status and safety data were collected for 30 days post treatment while mortality and disease progression were followed for 1 yr. An interim analysis by a data monitoring committee (DMC) was planned to assess safety and efficacy after 50% of pts completed the 30 day treatment period. A total of 390 pts who received melphalan (200 mg/m2) (n=239), BEAM (n=129), TBI (n=15), or other (n=7) were randomized and 384 pts were treated. The study drug was well tolerated in general and no pts discontinued study due to drug-related adverse events. There were 93 serious adverse events (SAEs) in 78 (20%) pts and no drug-related death was reported. Five infusion-related SAEs were reported including vasovagal episode (2), syncope (2), and anaphylactoid reaction (1). All 5 episodes occurred on the day of study drug infusion and resolved on the same day with no sequelae. Based on review of the results from the interim analysis, which included safety and efficacy data from 200 pts, the DMC recommended that the study continue to completion as planned. The last pt has completed the 30 day study period. The un-blinded results of the OM efficacy endpoints from velafermin treated groups or placebo as well as 30-day safety information from all pts will be reported.

scholarly journals Assessment of the Safety and Efficacy of a Raft-Forming Alginate Reflux Suppressant (Liquid Gaviscon) for the Treatment of Heartburn during Pregnancy

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Vicki Strugala ◽  
Julian Bassin ◽  
Valerie S. Swales ◽  
Stephen W. Lindow ◽  
Peter W. Dettmar ◽  
...  
Keyword(s):  
Adverse Events ◽  
Pregnant Women ◽  
Negative Impact ◽  
Normal Population ◽  
Patient Treatment ◽  
Controlled Study ◽  
Study Medication ◽  
Open Label ◽  
Safety And Efficacy ◽  
In Pregnancy

Gastro-oesophageal reflux (GER) and the symptoms of heartburn and regurgitation are common in pregnancy. These symptoms are transient and mostly resolve postpartum but have a negative impact on quality of life. Here, we present a prospective clinical evaluation of the safety and efficacy of an alginate raft-forming oral suspension that is licensed for use in pregnancy. The study was a multicentre, prospective, open-label, and baseline-controlled study of Liquid Gaviscon (LG) in the treatment of heartburn in pregnant women with current symptoms of heartburn and/or reflux requiring treatment (recruited 144). The efficacy of the study medication was rated by the investigator (primary endpoint) and patient. Treatment was deemed to be a success in 91% of patients as judged by the investigator (95% CI 85.0–95.3) and 90% (95% CI 84.1–94.8) when assessed by the patient themselves. Very few adverse events or serious adverse events were reported that were considered to be related to the study medication, and these were consistent with the normal population incidences. Serum sodium levels remained unchanged. This prospective open-label study in a large number of pregnant women has shown that LG is both safe and highly efficacious in the treatment of heartburn and GER symptoms in pregnancy.

Prophylaxis of neutropenia with mecapegfilgrastim in patients with non-myeloid malignancies in a real-world setting.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e24072-e24072
Author(s):  
Jun Ma ◽  
Huiqiang Huang ◽  
Peifen Fu ◽  
Nong Xu ◽  
Chenyu Mao ◽  
...  
Keyword(s):  
Adverse Events ◽  
Real World ◽  
Study Drug ◽  
Secondary Prophylaxis ◽  
Chemotherapy Cycle ◽  
Breast Cancer Patients ◽  
Continuous Administration ◽  
Real World Setting ◽  
Grade 3 ◽  
Long Acting

e24072 Background: The prophylaxis of neutropenia has been evolving from short acting granulocyte colony-stimulating factors (G-CSFs) to long acting G-CSFs. The safety and effectiveness of long acting G-CSF in a real-world setting were still lacking. Methods: We performed a multi-center, non-interventional, real-world study to explore the tolerability and effectiveness of mecapegfilgrastim. Different prophylactic strategy (primary or secondary prophylaxis) were compared. The effect of mecapegfilgrastim by means of continuous administration was also explored. Results: This study included 638 patients who had complete the study from May 2019 to November 15, 2020. About half of the participants were breast cancer patients. The mean age of the patients were 56 years. The most frequently reported adverse event possibly related to study drug was white blood cell increase (6.2 %). No unexpected adverse events were reported. Overall, thirty-six (5.6 %) patients experienced grade ≥ 3 neutropenia in chemotherapy cycle one. The patients in the primary and secondary prophylaxis subgroups had incidence of grade ≥ 3 neutropenia of 4.3 % and 9.2 % in chemotherapy cycle one respectively. There was a decreasing trend of neutropenia from cycle one to cycle four when mecapegfilgrastim were administrated continuously. Conclusions: The mecapegfilgrastim was well tolerable and no unexpected adverse events were observed in real-world setting. Primary prophylaxis using mecapegfilgrastim had lower incidence of neutropenia than secondary usage.

scholarly journals Safety and efficacy of herbal medicine for acute intracerebral hemorrhage (CRRICH): a multicentre randomised controlled trial

BMJ Open ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. e024932 ◽  
Author(s):  
Liling Zeng ◽  
Guanghai Tang ◽  
Jing Wang ◽  
Jianbin Zhong ◽  
Zhangyong Xia ◽  
...  
Keyword(s):  
Placebo Group ◽  
Herbal Medicine ◽  
Adverse Events ◽  
Intracerebral Haemorrhage ◽  
Poor Prognosis ◽  
Controlled Trial ◽  
Blood Stasis ◽  
Secondary Outcome ◽  
Controlled Study ◽  
Safety And Efficacy

ObjectiveTo evaluate the safety and efficacy of removing blood stasis (RBS) herbal medicine for the treatment of acute intracerebral haemorrhage (AICH) within a 6-hour time window.Study designA randomised, multicentre, double-blind, placebo-controlled study performed in 14 hospitals in China.Participants and interventionsPatients with AICH were randomly assigned to receive a placebo, the ICH-1 (Intracerebral Haemorrhage) formula (eight herbs, including the RBS herbs hirudo and tabanus) or the ICH-2 formula (six herbs without the RBS herbs hirudo and tabanus) within 6 hours of ICH onset.OutcomesThe primary safety outcome was the incidence of haematoma enlargement at 24 hours and at 10 days after treatment. The secondary outcome was the incidence of poor prognosis (mortality or modified Rankin Scale score ≥5) assessed at 90 days after symptom onset.ResultsA total of 324 subjects were randomised between October 2013 and May 2016: 105 patients received placebo; 108 patients received the ICH-1 formula; and 111 patients received the ICH-2 formula. The incidence of haematoma enlargement at 24 hours was 7.8% in the placebo group, 12.3% in the ICH-1 group and 7.5% in the ICH-2 group; the incidence of haematoma enlargement on day 10 was 1.1% in the placebo group, 1.1% in the ICH-1 group, and 3.1% in the ICH-2 group, with no significant differences among the groups (P>0.05). The mortality rates were 3.8% in the placebo group, 2.8% in the ICH-1 group, and 0.9% in the ICH-2 group; the incidences of poor prognosis were 7.1% in the placebo group, 6.0% in the ICH-1 group and 4.8% in the ICH-2 group at 3 months, with no significant differences among the groups (p>0.05). However, the overall frequency of treatment-emergent adverse events in the ICH-1 group (12.1%) was higher among the three groups (5.8% and 2.8%, respectively, p<0.05). All three cases of serious adverse events were in the ICH-1 group.ConclusionsUltra-early administration of ICH-1 formula for AICH patients did not exert significant beneficial effects on clinical outcomes but increased the risk of bleeding, which probably resulted from the inclusion of RBS herbal medicines in ICH-1.Trialregistration numberNCT01918722.

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