跳至主要内容
MedPath Trial logoMedPath TrialMedPath Trial Home
临床试验/NCT01074944
NCT01074944已完成3 期

A Phase 3, Randomized, Multi-Center, Multi-National, Double-Blind Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Once Daily Versus Twice Daily Dosing of Genz-112638 in Patients With Gaucher Disease Type 1 Who Have Demonstrated Clinical Stability on a Twice Daily Dose of Genz-112638

Genzyme, a Sanofi Company46 个研究点 分布在 17 个国家目标入组 170 人开始时间: 2010年6月最近更新:
Share to TwitterShare to FacebookShare to LinkedInShare to Reddit
适应症
干预措施
相关药物

试验速览

阶段
3 期
状态
已完成
发起方
入组人数
170
试验地点
46
主要终点
PAP: Percentage of Participants Who Remained Stable for 52 Weeks During the PAP
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The primary objective of this study was to evaluate the efficacy and safety of once daily (QD) versus twice daily (BID) dosing of eliglustat tartrate (Genz-112638) in participants with Gaucher disease type 1 who had demonstrated clinical stability on BID dosing of eliglustat tartrate (Genz-112638). The secondary objective was to evaluate the pharmacokinetics (PK) of Genz-99067 when eliglustat tartrate (Genz-112638) was administered QD and BID in participants with Gaucher disease type 1 who had demonstrated clinical stability on BID dosing of eliglustat tartrate (Genz-112638).

详细描述

NOTE: Other Phase 3 studies being conducted with eliglustat tartrate (Genz-112638) are GZGD02507 (ENGAGE): NCT00891202 and GZGD02607 (ENCORE): NCT00943111

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Treatment
盲法
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

入排标准

年龄范围
18 Years 至 —（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •The participant who was willing and provided signed informed consent prior to any study-related procedures.
  • •The participant was ≥18 years of age.
  • •The participant diagnosed with GD 1 confirmed by a documented deficiency of acid β-glucosidase activity by enzyme assay.
  • •Female participants of childbearing potential had a documented negative pregnancy test prior to administration of the first dose of eliglustat tartrate (Genz-112638) in this study. In addition, all female participants of childbearing potential used a medically accepted form of contraception throughout the study, i.e., either a barrier method or hormonal contraceptive with norethindrone and ethinyl estradiol or similar active components
  • •The participant met all of the following criteria at the time of screening: hemoglobin level ≥9 g/dL (mean of 2 measurements); platelet count ≥70,000/mm^3 (mean of 2 measurements); spleen volume ≤25 multiples of normal (MN); liver volume ≤2.0 MN.
  • •The participant consented to provide a blood sample for genotyping for Gaucher disease and for CYP2D6 to categorize the participant's predicted rate of metabolism, if these genotyping results were not already available for the participant.
  • •The participant was willing to abstain from consumption of grapefruit, grapefruit juice, or grapefruit products for 72 hours prior to administration of the first dose of Genz-112638 and throughout the duration of the study.

排除标准

  • •The participant was participating in GZGD02607 study, "A Phase 3, Randomized, Multi-Center, Multi-National, Open-Label, Active Comparator Study to Evaluate the Efficacy and Safety of Genz-112638 in Participants with GD1 who have been Stabilized with Cerezyme ® ," or was eligible for inclusion in GZGD02607 (while enrollment was ongoing) and had access to a physician participating in GZGD02607, or the participant was participating in GZGD02507 study, "A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study Confirming the Efficacy and Safety of Genz-112638 in Participants with GD1," or was eligible for inclusion in GZGD02507 (while enrollment was ongoing) and had access to a physician participating in GZGD
  • •The participant received miglustat within 6 months prior to administration of the first dose of Genz-112638 in this study.
  • •The participant had a partial or total splenectomy within 3 years prior to randomization.
  • •The participant received pharmacological chaperones or miglustat within 6 months prior to administration of the first dose of eliglustat tartrate (Genz-112638) in this study.
  • •The participant had any evidence of neurologic disorder (e.g., peripheral neuropathy, tremor, seizures, Parkinsonism or cognitive impairment) or pulmonary involvement (e.g., pulmonary hypertension) as related to Gaucher disease.
  • •The participant was transfusion-dependent.
  • •The participant had a documented deficiency of iron, vitamin B-12, or folate that requires treatment not yet initiated or, if initiated, the participant had not been stable under treatment for at least 3 months prior to administration of the first dose of Genz-112638 in this study.
  • •The participant had documented prior esophageal varices or clinically significant liver infarction or current liver enzymes (alanine transaminase [ALT]/aspartate aminotransferase [AST]) or total bilirubin >2 times the upper limit of normal (ULN), unless the participant had a diagnosis of Gilbert Syndrome.
  • •The participant had any clinically significant disease, other than Gaucher disease, including cardiovascular, renal, hepatic, gastrointestinal, pulmonary, neurologic, endocrine, metabolic (including hypokalaemia or hypomagnesemia), or psychiatric disease, other medical conditions, or serious intercurrent illnesses that, in the opinion of the Investigator, precluded participation in the study.
  • •The participant was known to have any of the following: Clinically significant coronary artery disease including history of myocardial infarction [MI] or ongoing signs or symptoms consistent with cardiac ischemia or heart failure; or clinically significant arrhythmias or conduction defect such as 2nd or 3rd degree AV block, complete bundle branch block, prolonged QTc interval, or sustained ventricular tachycardia (VT).
  • •The participant who tested positive for the human immunodeficiency virus (HIV) antibody, Hepatitis C antibody, or Hepatitis B surface antigen.
  • •The participant received an investigational product (other than eliglustat tartrate (Genz-112638)) within 30 days prior to administration of the first dose of eliglustat tartrate (Genz-112638) in this study.
  • •The participant was scheduled for in-participant hospitalization, including elective surgery, during the study.
  • •The participant had a history of cancer, with the exception of basal cell carcinoma, within 5 years prior to administration of the first dose of Genz-112638 in this study.
  • •The participant was pregnant or lactating.
  • •The participant had received any medication that may cause QTc interval prolongation within 30 days prior to the first dose of Genz-
  • •Exception: Diphenhydramine (Benadryl) or other medications used as premedication for ERT infusions were allowed up to 7 days prior to the first dose of Genz-
  • •The participant had received for the first time (i.e., the participant was not already chronically using) any of the following medications within 30 days prior to the first dose of Genz-112638:
  • •Strong inhibitors of CYP2D6 or CYP3A4;
  • •Inducers of CYP3A
  • •Exception: Premedications for ERT infusions were allowed up to 7 days prior to the first dose of Genz-
  • •The participant was a CYP2D6 non-poor metabolizer or an indeterminate metabolizer with one allele identified as active who was chronically receiving both a strong competitive inhibitor of CYP2D6 and a strong competitive inhibitor of CYP3A4 and for whom no reasonable alternative medication exists. or
  • •The participant was a CYP2D6 poor metabolizer or an indeterminate metabolizer with neither allele known to be active who was chronically receiving a strong competitive inhibitor of CYP3A4 and for whom no reasonable alternative medication exists.
  • •Exception for both cases: Premedications for ERT infusions were allowed up to 7 days prior to the first dose of Genz-112638.

研究组 & 干预措施

Twice Daily (BID) Dose Regimen

Experimental

Patients will receive either 50 mg BID or 100 mg BID

干预措施: Eliglustat tartrate (Drug)

Once Daily (QD) Dose Regimen

Experimental

Patients will receive either 100 mg QD or 200 mg QD

干预措施: Eliglustat tartrate (Drug)

结局指标

主要结局

PAP: Percentage of Participants Who Remained Stable for 52 Weeks During the PAP

时间窗: PAP Baseline up to the end of PAP (Week 52)

Participants were considered as stable if they met all of the following criteria: 1) no more than 2 bone crisis during PAP (with no more than 1 bone crisis during either the first 6 months or the later 6 months of the period), and were free of other clinically symptomatic bone disease during the entire 52-week PAP; 2) hemoglobin level not decreased \>1.5 g/dL from Baseline for PAP; 3) platelet count not decreased \>25% from Baseline for PAP; 4) spleen volume (in multiples of normal \[MN\]) did not increase \>25% from Baseline for PAP; 5) liver volume (in MN) did not increase \>20% from Baseline for PAP. Baseline for PAP was defined as the last assessment prior to randomization.

次要结局

  • PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52(Baseline, Week 26, Week 52)
  • PAP: Mean Platelet Count at Baseline, Weeks 26, 52(Baseline, Week 26, Week 52)
  • PAP: Mean Spleen Volume at Baseline, Weeks 26, 52(Baseline, Week 26, Week 52)
  • PAP: Mean Liver Volume at Baseline, Weeks 26, 52(Baseline, Week 26 and Week 52)
  • PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52(Baseline, Week 26, Week 52)
  • PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26 and Week 52(Baseline, Week 26 and week 52)
  • PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52(Baseline, Week 26, Week 52)
  • PAP: Total T-Scores for BMD at Baseline and Week 52(Baseline, Week 52)
  • PAP: Total Z-scores for BMD at Baseline and Week 52(Baseline, Week 52)
  • PAP: Bone Mineral Density (BMD) at Baseline and Week 52(Baseline, Week 52)
  • PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52.(Baseline, Week 26 and Week 52)
  • LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78(Baseline, Week 26, Week, 52, and Week 78)
  • PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52(Baseline, Week 26, and Week 52)
  • PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52(Baseline, Week 26, and Week 52)
  • PAP: Total Bone Marrow Burden Score (BMB) at Baseline and Week 52(Baseline, Week 52)
  • LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78(Baseline, Week 26, Week 52, Week 78)
  • LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78(Baseline, Week 26, Week 52, Week 78)
  • LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78(Baseline, Week 26, Week 52, Week 78)
  • LIP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26, 52, and 78(Baseline, Week 26, Week 52 and Week 78)
  • LIP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26, Week 52, and Week 78(Baseline, Week 26, Week 52 and Week 78)
  • LIP: Mean Biomarker (MIP1-beta) Value at Baseline, Week 78(Baseline and Week 78)
  • LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78(Baseline, Week 26, Week 52, Week 78)
  • LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78(Baseline, Week 26, Week 52, Week 78)
  • LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78(Baseline, Week 26, Week 52, Week 78)
  • LTTP: Percentage of Participants Who Maintained a Stable Bone Criterion ,Hemoglobin Level, Platelet Count, Liver Volume and Spleen Volume at 1 Year and 2 Years(1 Year, 2 Years)
  • LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years(Baseline, 1 year, and 2 years)
  • LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years(Baseline, 1 year and 2 years)
  • LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years(Baseline, 1 year and 2 years)
  • LTTP: Bone Mineral Density (BMD) at Baseline, 1 Year, and 2 Years(Baseline, 1 year, and 2 years)
  • LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years(Baseline, 1 year, and 2 years)
  • LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years(Baseline, 1 year, and 2 years)
  • LTTP: Total Bone Marrow Burden Score (BMB) at Baseline, 1 Year, and 2 Years(Baseline, 1 year, and 2 years)
  • LTTP: Mean Biomarker (Chitotriosidase) Value at Baseline, 1 Year, and 2 Years(Baseline, 1 year, and 2 years)
  • LTTP: Mean Biomarker (GL-1 on DBS) Value at Baseline, 1 Year, and 2 Years(Baseline, 1 year, and 2 years)
  • LTTP: Mean Biomarker (MIP1-beta) Value at Baseline, 1 Year, and 2 Years(Baseline, 1 year, and 2 years)

研究者

发起方
Genzyme, a Sanofi Company
申办方类型
Industry
责任方
Sponsor

研究点 (46)

Loading locations...

相似试验

已完成
3 期
Efficacy and Safety of IDP-121 and IDP-121 Vehicle Lotion in the Treatment of Acne VulgarisAcne
NCT02965456Bausch Health Americas, Inc.820
已完成
3 期
Efficacy and Safety of IDP-121 and IDP-121 Vehicle Lotion in the Treatment of Acne VulgarisAcne
NCT02932306Bausch Health Americas, Inc.820
Unknown
2 期
Study to Compare the Safety and Efficacy of IDP-123 Lotion to Tazorac Cream in the Treatment of Acne VulgarisAcne Vulgaris
NCT02525822Valeant Pharmaceuticals210
已完成
3 期
Efficacy and Safety of Dexlansoprazole MR and Lansoprazole on Healing of Erosive EsophagitisEsophagitis, RefluxEsophagitis, Peptic
NCT00251693Takeda2,038
已完成
3 期
A 42-day Parallel Group Safety Study of Revefenacin and Formoterol, Administered in Sequence and as a Combination, in Participants With COPDChronic Obstructive Pulmonary Disease (COPD)
NCT03573817Mylan Inc.122