Bevacizumab biosimilar and reference bevacizumab in subjects with stage IIIB/IV no squamous non-small cell lung cancer (NSCLC) (STELLA study): Results for the primary endpoint in a confirmatory, double-blind, randomized, controlled study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21542-e21542
Author(s):  
Susana Millan ◽  
Dmytro Trukhin ◽  
Oleksii Kolesnik ◽  
Elena Poddubskaya ◽  
Andric Zoran ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Objective Response ◽  
Stage Iiib ◽  
Study Endpoint ◽  
Controlled Study ◽  
Primary Study ◽  
Double Blind ◽  
Study Results ◽  
Significant Difference ◽  
Secondary Endpoints

e21542 Background: MB02 is a proposed biosimilar of the reference bevacizumab. A multinational, double-blind, randomized, parallel group clinical study (STELLA) is undergoing to confirm clinical similarity between MB02 and bevacizumab in patients with stage IIIB/IV no squamous NSCLC. Methods: Subjects were randomized 1:1 to MB02 or bevacizumab (15 mg/kg) plus chemotherapy (paclitaxel [P] 200 mg/m2 and carboplatin [C] AUC6) on Day 1 of every 3-week cycle for 6 cycles (Week 18) followed by MB02/bevacizumab in blinded monotherapy until disease progression, treatment intolerance, death, patient withdrawal or end of study (Week 52). As primary study endpoint, the efficacy by means of the objective response rate (ORR) evaluated by an independent radiological committee (IRC) was compared between arms at Week 18. Secondary endpoints were Progression Free Survival (PFS) and Overall Survival (OS), safety and immunogenicity (assessed at 18 and 52 weeks). Results: 627 patients were randomized: MB02 (n = 315) and bevacizumab (n = 312). Demographic and baseline characteristics were well balanced between arms. The ORR results were comparable for subjects receiving MB02 or bevacizumab plus P/C. A Risk Ratio (RR) of 1.013 (90% CI: -0.037% to 0.059) and a Risk Difference (RD) of 0.011 (90% CI: -0.037% to 0.059), were within the similarity margin predefined by FDA (0.73, 1.36) and EMA (-12%, +12%) respectively. This ORR assessed by IRC was consistent with the investigator assessment criteria. There was no significant difference between arms for secondary efficacy endpoints (PFS/OS) at week 18. Up to primary endpoint cut-off point, the safety assessment showed no significant differences between MB02 and bevacizumab arms (including the immunogenicity assessment) in terms of nature, frequency and severity of the adverse events (AE), being anaemia and hypertension the most common IMP-related AEs, with a RD between treatment groups < 5%. New signals or observable trends were no reported for MB02-treated subjects. Additional information on the secondary endpoints will be available at week 52 (end of monotherapy period). Conclusions: The statistical analysis executed for ORRs confirm the equivalence of MB02 and bevacizumab, supporting the clinical activity of MB02 treatment. MB02 was well tolerated with manageable AEs in patients with Stage IIIB/IV NSCLC. Clinical trial information: NCT03296163.

Updated results of European Organization for Research and Treatment of Cancer (EORTC) phase 2 trial 1202 cabazitaxel in patients with metastatic or inoperable locally advanced dedifferentiated liposarcoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11518-11518
Author(s):  
Roberta Sanfilippo ◽  
Richard L Hayward ◽  
Jammbe Musoro ◽  
Charlotte Benson ◽  
Michael Gordon Leahy ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Objective Response ◽  
Locally Advanced ◽  
Phase Iii ◽  
Dedifferentiated Liposarcoma ◽  
Study Endpoint ◽  
Primary Study ◽  
Primary Analysis ◽  
European Organization ◽  
Experimental Drugs

11518 Background: Treatment options for patients with unresectable and/or metastatic dedifferentiated liposarcoma (DDLPS) are limited. The most effective agents include doxorubicin, ifosfamide, trabectedin and eribulin, but, in general, objective response rates (ORR) and progression free survival (PFS) are modest. Cabazitaxel exerts its effect through inhibition of microtubular disassembly and has been shown to be relatively safe, effective and well-tolerated. EORTC 1202 assessed whether cabazitaxel demonstrated sufficient antitumor activity in patients with metastatic or inoperable locally advanced DD LPS to justify further investigation in a phase III setting. Methods: This was an international multi-center, open label single arm phase II trial. The clinical cut-off date for the primary analysis was performed on August 31, 2020. Data base lock was performed on February 2, 2021. Eligible patients with metastatic or inoperable locally advanced DD LPS, after a centralized pathological review, were treated with cabazitaxel 25mg/m² IV infusion over 1 hour every 21 days. Primary endpoint was PFS rate at 12 weeks assessed by local investigator per RECIST 1.1. Based on a Simon two-stage design, at least 4 out of 17 (Stage 1) and 11 out of 37 (Stage 2) eligible and evaluable patients who are progression-free at 12 weeks were needed. Currently, a centralized radiological assessment is ongoing. Results: Forty patients were registered by 10 institutions in 4 countries between March 2015 and March 2019, with 2 patients being ineligible. One patient was still on treatment at the clinical cut-off date. The number of cycles ranged from 1 to 30, with a median of 5; 26 patients (65%) received at least 4 cycles of cabazitaxel. PFS at 12 weeks was 55% (conditional 1-sided 95% CI 40.8-100), achieving the primary study endpoint. The median FU was 21.6 months, median PFS was 6 months and median OS 21 months. RR was 8% with one CR and two PR. Twenty-three(60.5%) pts had a SD. Disease control (PR+SD) was achieved in 26 patients (68%). The most common cabazitaxel -related grade >3 adverse events in all 40 registered patients were Neutrophil count decreased (50%), febrile neutropenia (25%), fatigue (12.5%), and anemia (10%). There were no cabazitaxel-related deaths. Conclusions: EORTC 1202 met its primary endpoint, with 21/38 pts (55%) being progression-free at 12 weeks. Results of this trial confirm activity of cabazitaxel in patients with metastatic or inoperable locally advanced DD LPS and looks interesting if compared to the other available options and experimental drugs recently reported in this patient population. Clinical trial information: NCT01913652.

UW-01: A randomized comparison of three doses of weekly docetaxel as 1st-line chemotherapy in stage IV breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10522-10522
Author(s):  
J. R. Gralow ◽  
D. Chielens ◽  
G. Schuster ◽  
B. Storer ◽  
M. J. McCleod ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stage Iv ◽  
Phase Iii ◽  
Study Endpoint ◽  
Primary Study ◽  
Hematologic Toxicity ◽  
Stage Iv Breast Cancer ◽  
Study Results ◽  
Significant Difference ◽  
Grade 3

10522 Background: Docetaxel (DOC) is an active agent in the treatment of breast cancer. The optimal dose and dosing interval for DOC, with respect to balancing efficacy and toxicity, has yet to be determined. In this multi-center, randomized phase III trial, we attempted to compare 3 doses of single-agent weekly DOC. Methods: Patients with documented evaluable or measurable stage IV breast cancer and no prior metastatic chemotherapy were eligible. Prior adjuvant chemotherapy was permitted if ≥ 6 months had elapsed. Adjuvant exposure to DOC was allowed if ≥ 1 year prior. All patients received intravenous weekly DOC, 3 out of 4 weeks. Patients on Arm A received doses of 25 mg/m2, Arm B received 30 mg/m2, and Arm C received 35 mg/m2. The primary study outcome was time to progression (TTP). Secondary endpoints included toxicity, response rate (RR), and overall survival (OS). Targeted accrual was 600 patients. Results: The study was stopped early for feasibility reasons (poor accrual) after a total of 108 patients were enrolled at 49 U.S. sites. The median patient age was 63 years. Grade 3, 4 non-hematologic toxicity was 22%, 22%, and 23% in Arms A, B and C respectively. Nail toxicity of any grade occurred in 2 patients in Arm A, 6 patients in Arm B, and 7 patients (2 of which were grade 3) in Arm C. TTP for Arm A was 19 weeks (95% confidence intervals [CI] 10–23), 28 weeks for Arm B (95% CI 15–38), and 24 weeks for Arm C (95% CI 12–37). There was a marginally significant difference in TTP between arms A and C (HR = 1.7, 95% CI = 1.0–2.8, p = 0.05), but not between arms B and C (HR = 1.0, 95% CI 0.6–1.7, p = 0.94). RR was 26%, 27%, and 31% in Arms A, B and C, respectively. Median survival was 77 weeks for Arm A (95% CI 53–115), and 96 weeks for arm B (95% CI 53-undetermined); it has not yet been reached for Arm C. Discussion: The interpretation of study results is limited due to early stopping and resultant loss of statistical power. For the primary study endpoint, TTP, the lowest (25 mg/m2) dose may be less than optimal, but there was no observed difference between the intermediate (30 mg/m2) and highest doses (35 mg/m2) of weekly DOC. Grade 3, 4 non-hematologic toxicities were similar between the 3 arms. [Table: see text]

A phase III, randomized, double-blind, placebo (Pla)-controlled study of pertuzumab (P) + trastuzumab (H) + docetaxel (D) versus Pla + H+ D in previously untreated HER2-positive locally recurrent/metastatic breast cancer (LR/MBC) (PUFFIN).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1026-1026 ◽  
Author(s):  
Binghe Xu ◽  
Wei Li ◽  
Qingyuan Zhang ◽  
Shao Zhimin ◽  
Wang Xiao Jia ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Objective Response ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Controlled Study ◽  
Her2 Positive ◽  
Double Blind ◽  
Ventricular Ejection Fraction

1026 Background: In CLEOPATRA (NCT00567190), adding P to H + D significantly improved progression-free and overall survival (PFS/OS) v Pla + H + D in patients (pts) with previously untreated HER2-positive LR/MBC. PUFFIN (NCT02896855) is a China bridging study; the objective being to assess consistency of efficacy with CLEOPATRA. Methods: Pts with previously untreated HER2-positive LR/MBC were randomized 1:1 to P + H + D or Pla + H + D, stratified by visceral v non-visceral disease and hormone receptor status. The primary endpoint was investigator-assessed PFS. Secondary endpoints included objective response rate (ORR in pts with measurable baseline disease), OS, and safety. The target sample size (240) was determined based on the consistency threshold for PFS, defined as hazard ratio (HR) < 0.81, which maintains ≥ 50% of the risk reduction determined in CLEOPATRA (HR 0.62). Results: Two hundred forty-three pts were randomized. Baseline/disease characteristics and prior therapies were generally balanced between arms. For PFS, the HR was 0.69 (95% CI 0.49, 0.99) in the ITT population. No cases of heart failure or symptomatic left ventricular ejection fraction decline were reported. Efficacy/safety are shown in the table. Conclusions: PUFFIN met its primary endpoint. Overall, efficacy data were consistent with CLEOPATRA (ITT population and Asian subgroup). Safety was also consistent and in line with the known P safety profile, with no new or unexpected signals reported. PUFFIN adds to the totality of data with P in previously untreated HER2-positive LR/MBC, and supports the favorable benefit–risk profile of P in Chinese pts. Clinical trial information: NCT02896855. [Table: see text]

Cyclandelate in the Prophylaxis of Migraine: A Placebo-Controlled Study

Cephalalgia ◽  
2001 ◽  
Vol 21 (1) ◽  
pp. 66-70 ◽  
Author(s):  
HC Diener ◽  
P Krupp ◽  
T Schmitt ◽  
G Steitz ◽  
K Milde ◽  
...  
Keyword(s):  
Baseline Period ◽  
Migraine Prophylaxis ◽  
Study Endpoint ◽  
Controlled Study ◽  
Primary Study ◽  
Parallel Group ◽  
Primary Study Endpoint ◽  
Placebo Phase ◽  
Secondary Endpoints ◽  
Autonomic Disturbances

The prophylactic action of cyclandelate was investigated in a multicentre, randomized, placebo-controlled, parallel group study. A 4-week baseline period was followed by a 4-week placebo phase and a 16-week treatment period with either 1600 mg cyclandelate or placebo. Patients ( n = 251) with two to six migraine attacks/month were randomized. Neither the primary study endpoint (reduction of migraine days from baseline to the last 28 days) nor most of the secondary endpoints (reduction in the number of migraine attacks, severity or duration of attacks, frequency of autonomic disturbances, medication for treatment of attacks) showed a difference between cyclandelate and placebo. Cyclandelate, however, was superior to placebo in a global impression of efficacy rated by the patients and the treating physicians. Both treatments were well tolerated. In conclusion, cyclandelate was not superior to placebo in the prophylaxis of migraine with regard to parameters usually used in migraine prophylaxis trials.

Cetuximab with or without sorafenib in recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6047-6047 ◽  
Author(s):  
Jill Gilbert ◽  
Michael J. Schell ◽  
Xiuhua Zhao ◽  
Barbara A. Murphy ◽  
Tawee Tanvetyanon ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Single Agent ◽  
Infusion Reaction ◽  
Study Endpoint ◽  
Controlled Study ◽  
Primary Study ◽  
Clinical Activity ◽  
Patients Âgés ◽  
Significant Difference ◽  
The Mean

6047 Background: For patients with R/M SCCHN, cetuximab, a monoclonal antibody against EGFR, is approved as a single agent and has a survival benefit when combined with chemotherapy. We hypothesized that addition of sorafenib, a multi-kinase inhibitor of targets including VEGFR, to cetuximab may have greater clinical benefit than cetuximab alone. Methods: This trial was designed as a blinded, randomized phase II, placebo-controlled study of cetuximab at 400 mg/m2 IV on day 1 followed by 250 mg/m2 IV weekly plus placebo bid (Arm A) or cetuximab at the same dose and schedule plus sorafenib 400 mg po bid (Arm B), each in 21 day cycles. After 19 patients were enrolled, the trial was amended to remove the placebo (and blinding) due to issues with placebo tablet solubility. Target sample size was 84 patients with 83% power to detect a 2-month increase in PFS, the primary study endpoint. Interim analysis was planned at midpoint, requiring hazard ratio < 1 to proceed to the second stage of study. Serum cytokine and tumor HPV ISH and p16 analyses were performed. Results: Of 56 patients (ages 26-74, 80% male) enrolled, 53 patients received treatment and 41 were evaluable for response. Of the patients who received therapy, 26 received cetuximab only (Arm A). For Arm A, the mean number of cycles delivered was 4.3 (range 1-16) and the mean for Arm B was 3.3 (range 1-11). The most common grade 3/4 AEs were fatigue (2 A, 1 B), hypertension (3 B), infusion reaction (both arms), and diarrhea (2 B). Arm A had 2 PRs and Arm B had 4 PRs. Median OS was 7 mo and 5.9 mo respectively. Median PFS was 3.1 mo for both arms. 24 patients had pre-treatment cytokine measurements. Of the 12 measured cytokines, high TGFB1 level was significantly correlated with inferior PFS (4.6 mo vs 1.6 mo), regardless of arm (p=0.015). 38 patients had tumors available for p16 staining (31 neg and 7 pos). 3 of 7 p16 pos were also HPV ISH pos. The p16 neg patients had significantly improved PFS (3.5 mo vs 1.6 mo) regardless of arm (p=0.032) but no difference in OS (p=1.0). Conclusions: Both arms demonstrated clinical activity although no significant difference was observed. However, a subset of patients with p16 neg tumors or low serum TGFB1 may have a greater benefit with cetuximab-based therapy. Clinical trial information: NCI-2012-02847.

A phase II randomized placebo-controlled study investigating the combination of yiv-906 and sorafenib (SORA) in HBV (+) patients (Pts) with advanced hepatocellular carcinoma (HCC).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS601-TPS601
Author(s):  
James J. Harding ◽  
Ghassan K. Abou-Alfa ◽  
Yuankai Shi ◽  
Jacqueline Whang-Peng ◽  
Man Fung Yuen ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Performance Status ◽  
Objective Response ◽  
Tumor Rejection ◽  
Controlled Study ◽  
Advanced Hepatocellular Carcinoma ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Advanced Hcc ◽  
Potential Clinical Benefit

TPS601 Background: First-line systemic treatment options for advanced HCC pts are limited to the multi-targeted tyrosine kinase inhibitors, SORA and lenvatinib. Both agents improve outcomes for pts with advanced disease, but are associated with increased rate of grade ≥ 3 treatment-related adverse events. YIV-906 (PHY906, KD018) is derived from Huang-Qin-Tang, a traditional Chinese medicine documented 1800 years ago to treat gastrointestinal ailments. Preclinical data indicate YIV-906 increases inflammation in the tumor microenvironment by M1 macrophages activation/proliferation resulting in HCC tumor rejection in vivo and reduces SORA associated toxicity. Clinical experience with YIV-906 plus SORA suggests safety and potential clinical benefit to HCC pts with chronic HBV infection. Methods: This is a proof-of-concept, international, multicenter, double-blind, placebo-controlled, randomized phase 2 study designed to compare the efficacy of YIV-906 and SORA to SORA alone in advanced HCC pts (NCT04000737). Key eligibility criteria include age ≥ 18 years, HBV-associated HCC, ≥ 1 measurable untreated lesion, Child-Pugh A liver function, and no prior systemic therapy. An estimated 125 pts will be randomized 2:1 to receive the investigational (YIV-906 plus SORA) or control (placebo plus SORA) arm until disease progression or unacceptable toxicity. Pts will be stratified by metastatic status (extrahepatic/vascular invasion vs none) and ECOG performance status (0 vs. 1). The primary endpoint is progression-free survival (PFS). Secondary endpoints include objective response rate and disease control rate by mRECIST, time to progression, overall survival, quality of life, and safety by CTCAE version 4.0. Translational correlatives include pharmacokinetics, effects on oral/gut microbiota, and exploratory soluble biomarkers analysis. For the primary endpoint, sample size of 41 pts in control arm and 84 pts in the investigational arm achieves 90% power at a 0.05% significance level to detect a hazard ratio of 0.5 assuming the median PFS of the control SORA arm is 3.6 months and that of the combination arm is 7.3 months. Clinical trial information: NCT04000737.

scholarly journals Prospective, Randomized, Double Blind, Multicenter Study for an Autocrosslinked Polysaccharide Gel to Evaluate Antiadhesive Effect and Safety Compared to Poloxamer/Sodium Alginate After Thyroidectomy

2019 ◽  
Vol 103 (9) ◽  
pp. 452-460
Author(s):  
Woo Young Kim ◽  
Jae Bok Lee ◽  
Hoon Yub Kim ◽  
Pyoung Jae Park ◽  
Seung Pil Jung ◽  
...  
Keyword(s):  
Sodium Alginate ◽  
Primary Endpoint ◽  
Esophageal Motility ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Significant Difference ◽  
Secondary Endpoints ◽  
Double Blinded ◽  
Voice Range

The aim of the study was to compare the efficacy and safety between an autocrosslinked polysaccharide (ACP) gel (Hyalobarrier) and a poloxamer/sodium alginate (P/SA: Guardix-SG) in preventing adhesions after thyroidectomy and demonstrate the noninferiority of ACP gel to P/SA. To identify differences of antiadhesive efficacy and safety between the ACP gel and P/SA, we investigated various variables such as the proportion of normal esophageal motility as assessed using marshmallow esophagography, swallowing impairment, adhesion severity and so on. This prospective, randomized, double-blinded, multicenter, phase III study investigated the antiadhesive efficacy and safety of ACP gel compared with those of P/SA for 12 weeks. Subjects were randomly assigned to receive either ACP gel (n = 97) or P/SA (n = 96). The primary endpoint was the proportion of normal esophageal motility as assessed using marshmallow esophagography, while the secondary endpoints included swallowing impairment, adhesion severity, laryngoscopic assessment of the vocal cords, and voice range profile. Safety endpoints included adverse events. There was no significant difference between the ACP gel and P/SA groups in the proportion of normal esophageal motility as the primary endpoint (P = 0.7428). In addition, there were no differences in the secondary or safety endpoints between the 2 groups. It was demonstrated that ACP gel was not inferior to P/SA. ACP gel appears both effective and safe for use in preventing adhesions after thyroidectomy.

TIME: A phase IIb/III randomized, double-blind, placebo-controlled study comparing first-line therapy with or without TG4010 immunotherapy product in patients with stage IV non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS7610-TPS7610 ◽  
Author(s):  
Elisabeth A. Quoix ◽  
John J. Nemunaitis ◽  
Tomasz Burzykowski ◽  
Berangere Bastien ◽  
Gisele Lacoste
Keyword(s):  
Primary Endpoint ◽  
Stage Iv ◽  
Predictive Biomarker ◽  
Phase Iii ◽  
Controlled Study ◽  
First Line ◽  
Double Blind ◽  
First Line Therapy ◽  
Line Therapy ◽  
Study Results

TPS7610 Background: TG4010 is an immunotherapy product based on a poxvirus (MVA) coding for the MUC1 tumor-associated antigen and interleukin-2. A previous study, TG4010.09, which evaluated the combination of first-line chemotherapy with and without TG4010 in advanced NSCLC, achieved its primary endpoint based on 6-month progression-free survival (PFS) and showed that the pre-treatment level of activated Natural Killer (aNK) cells may be a potential predictive biomarker for TG4010 efficacy (E. Quoix et al., Lancet Oncol. 2011;12:1125-33). Methods: TIME is a double-blind phase IIb/III study comparing the combination of first-line therapy with TG4010 or placebo in stage IV NSCLC patients, Performance Status (PS) 0 or 1 with a MUC1 expressing tumor by immunohistochemistry. The Phase IIb part of the study aims at prospectively validating aNK level as a predictive biomarker with PFS as a primary endpoint, by comparing the two treatment arms in two subgroups defined according to the level of aNK cells at baseline (normal or high). Bayesian criteria, derived from the TG4010.09 study results, will be used to confirm that, with a large probability, the true hazard ratio is <1 in patients with normal level of aNK cells and >1 in patients with high level of aNK cells. The Phase III part of the study will then compare, by using a frequentist approach, the two treatment arms with overall survival as a primary endpoint in the patient population confirmed to be of interest in the Phase IIb part. The phase III part is powered to detect a 27% reduction in the hazard rate of death. Phase IIb and III parts of the study will enroll respectively 206 and 800 patients. A dynamic minimization procedure will be applied at randomization for histology, prescription of bevacizumab, type of chemotherapy, PS and center. If qualifying for, patients will receive maintenance therapy after chemotherapy according to labeling. The study TIME is open to recruitment and referenced in ClinicalTrials.gov with the identifier NCT01383148.

scholarly journals Phase 3 randomized, placebo-controlled study of galcanezumab in patients with chronic cluster headache: Results from 3-month double-blind treatment

Cephalalgia ◽  
2020 ◽  
Vol 40 (9) ◽  
pp. 935-948 ◽  
Author(s):  
David W Dodick ◽  
Peter J Goadsby ◽  
Christian Lucas ◽  
Rigmor Jensen ◽  
Jennifer N Bardos ◽  
...  
Keyword(s):  
Cluster Headache ◽  
Injection Site ◽  
Treatment Period ◽  
Primary Endpoint ◽  
Baseline Period ◽  
Chronic Cluster Headache ◽  
Controlled Study ◽  
Attack Frequency ◽  
Double Blind ◽  
Secondary Endpoints

Objective To report efficacy and safety of galcanezumab in adults with chronic cluster headache. Background Galcanezumab is a humanized monoclonal antibody that binds to calcitonin gene-related peptide and inhibits its biological activity. Methods This study comprised a prospective baseline period, a 12-week double-blind, placebo-controlled treatment period, and a 52-week open-label period. Up to six protocol-specified concomitant preventive medications were allowed if patients were on a stable dose for 2 months prior to the prospective baseline period. Patients were randomized 1:1 to monthly subcutaneous galcanezumab (300 mg) or placebo. The primary endpoint was overall mean change from baseline in weekly attack frequency with galcanezumab compared to placebo. Key secondary endpoints were ≥50% response rate and percentage of patients meeting sustained response. Results from the double-blind treatment period are reported. Results A total of 237 patients were randomized and treated (120 placebo; 117 galcanezumab). At baseline, the mean age was 45 years and 63% were using ≥1 preventive drug. The primary endpoint was not met; mean change in weekly attack frequency was −4.6 placebo versus −5.4 galcanezumab ( p = 0.334). Key secondary endpoints also were not met. Injection site-related treatment-emergent adverse events were more common in the galcanezumab than the placebo group, with significantly more injection site erythema. Conclusion Treatment with galcanezumab 300 mg did not achieve its primary and key secondary endpoints. This study underscores the potential distinct biology of cCH as well as the significant unmet need for safe, effective, and well-tolerated preventive treatment. The safety profile of galcanezumab in cCH is consistent with that observed in trials of episodic CH and migraine. Trial registration NCT02438826; https://www.clinicaltrials.gov/ct2/show/NCT02438826 .

Efficacy and Tolerability of Amitriptylinoxide in the Treatment of Chronic Tension-Type Headache: A Multi-Centre Controlled Study

Cephalalgia ◽  
1994 ◽  
Vol 14 (2) ◽  
pp. 149-155 ◽  
Author(s):  
V Pfaffenrath ◽  
H-C Diener ◽  
H Isler ◽  
C Meyer ◽  
E Scholz ◽  
...  
Keyword(s):  
Adverse Events ◽  
Tension Type Headache ◽  
Study Endpoint ◽  
Controlled Study ◽  
Primary Study ◽  
Chronic Tension Type Headache ◽  
Headache Intensity ◽  
Primary Study Endpoint ◽  
Significant Difference ◽  
Type Headache

Amitriptyline is the medication of first choice in the treatment of chronic tension-type headache. In 197 patients with chronic tension-type headache (87M and 110F with a mean age of 38 ±13 (18–68)) efficacy and tolerability of 60–90 mg amitriptylinoxide (AO) were compared with 50–75 mg amitriptyline (AM) and placebo (PL) in a double-blind, parallel-group trial consisting of a four weeks' baseline phase and 12 weeks of treatment. The primary study endpoint was a reduction of at least 50% of the product of headache duration and frequency and a reduction of at least 50% in headache intensity. Statistics used were Fisher's exact test and analysis of variance. No significant difference emerged between AO, AM and PL with respect to the primary study endpoint. Treatment response occurred in 30.3% of the AO, 22.4% of the AM and 21.9% of the PL group. A reduction in headache duration and frequency of at least 50% was found in 39.4% on AO, in 25.4% on AM and in 26.6% on PL (PAO-PL = .1384, PAM-PL = 1.000, PAO-AM = .0973). A reduction in headache intensity of at least 50% was found in 31.8% on AO, in 26.9% on AM and in 26.6% on PL (PAO-PL = .5657, PAM-PL = 1.000, PAO-AM = .5715). Trend analysis with respect to a significant reduction of headache intensity ( p < 0.05) and the product of headache duration and frequency revealed a superior effect of AO. Adverse events occurred in 75.8% on AO, 82.1% on AM and 76.6% on PL (PAO-PL = 1.000, PAM-PL =.5188, PAO-AM = .4017). Neither depressive symptoms, measured by the SCL-90-R, nor study drug-related adverse events had any influence on the results.

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