Phase III, Multicentre, Open Study to Assess the Efficacy and Safety Profiles of the Co-administration of Lanreotide Autogel 120 mg (Administered Via Deep Subcutaneous Injections Every 28 Days) and Pegvisomant 40 to 120 mg Per Week (Administered Via Subcutaneous Route Once or Twice a Week) in Acromegalic Patients Failing to Respond to Lanreotide Autogel 120 mg Alone
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Ipsen
- 入组人数
- 125
- 试验地点
- 24
- 主要终点
- Percentage of Subjects With Acromegaly With a Normalised (Age and Sex Adjusted) IGF-1 Level at the End of the Co-administration Period
研究概览
简要总结
The main aim of this study is to assess the efficacy of the co-administration of lanreotide Autogel 120 mg (administered via deep sub-cutaneous injections every 28 days) and pegvisomant (administered at 40 to 120 mg per week via sub-cutaneous injection given once or twice a week) on IGF-1 levels over 28 weeks in acromegalic patients. The primary endpoint will be the percentage of acromegalic patients with normalised (age and sex adjusted) IGF-1 level at the end of the co-treatment period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient must have had documentation supporting the diagnosis of acromegaly, including elevated GH and/or IGF-1 levels
- •The patient is treated with pegvisomant, because of IGF-1 level remaining above ULN when treated with somatostatin analogue, on a daily basis for at least 3 months and has normal (age and sex adjusted) IGF-1 level, or IGF-1 level above the upper limit of normal (ULN) after treatment with pegvisomant 30 mg per day, OR the patient is treated with lanreotide Autogel or octreotide LAR for at least 6 months including 3 months at the highest marketed dose and has a serum IGF-1 level above ULN, 28 days after the last injection
- •At the end of the run-in period, The patient has a serum IGF-1 level above 1.2 x ULN, or a serum IGF-1 level between ULN and 1.2 x ULN and a serum GH nadir > 1 µg/L (assessed by an OGTT), 28 days after the 3rd injection of lanreotide Autogel 120 mg OR the patient is diabetic and has a serum IGF-1 level above 1.2 ULN, 28 days after the 3rd injection of lanreotide Autogel 120 mg
排除标准
- •The patient has undergone pituitary surgery or radiotherapy within 6 months prior to study entry, or it is anticipated that it will be done during the study
- •The patient has already been treated with a somatostatin analogue associated with a GH antagonist
- •The patient has received dopamine agonist within 6 weeks prior to the study entry
- •The patient has abnormal hepatic function at study entry (defined as AST, ALT, GGT, alkaline phosphatase, prothrombin time or total bilirubin above 2 ULN)
- •The patient is at risk of pregnancy or is lactating
研究组 & 干预措施
1
干预措施: lanreotide (Autogel formulation) (Drug)
1
干预措施: Pegvisomant (Drug)
结局指标
主要结局
Percentage of Subjects With Acromegaly With a Normalised (Age and Sex Adjusted) IGF-1 Level at the End of the Co-administration Period
时间窗: V3 (Week 12; Baseline) up to V11 (Week 44)
Serum IGF-1 is a well known and validated marker of acromegaly. IGF-1 assessments were performed at Visit (V) 1, V2, V3, V5, V7, V9 and V11 (or in case of premature study discontinuation, at the early withdrawal visit) and were based on a single serum sample taken in fasting conditions, prior to investigational medicinal product (IMP) administration. Percentage of subjects with a normalised (age and sex adjusted) IGF-1 level at the end of the co-administration period are presented. The last observation carried forward (LOCF) was used to replace missing IGF-1 values.
Percentage of Subjects With Acromegaly With a Normalised (Age and Sex Adjusted) IGF-1 Level at the End of the Co-administration Period; Summarised by Diabetic Status at Baseline
时间窗: V3 (Week 12; Baseline) up to V11 (Week 44)
Serum IGF-1 is a well known and validated marker of acromegaly. IGF-1 assessments were performed at V1, V2, V3, V5, V7, V9 and V11 (or in case of premature study discontinuation, at the early withdrawal visit) and were based on a single serum sample taken in fasting conditions, prior to IMP administration. Percentage of subjects with a normalised (age and sex adjusted) IGF-1 level at the end of the co-administration period, summarised by diabetic status are presented. The denominator used to calculate percentages was the number of subjects in each subgroup (diabetic and non diabetic). The LOCF approach was used to replace missing IGF-1 values.
Percentage of Subjects With Acromegaly With a Normalised (Age and Sex Adjusted) IGF-1 Level at the End of the Co-administration Period; Summarised by Previous Treatment and by Final Dose of Pegvisomant
时间窗: V3 (Week 12; Baseline) up to V11 (Week 44)
Serum IGF-1 is a well known and validated marker of acromegaly. IGF-1 assessments were performed at V1, V2, V3, V5, V7, V9 and V11 (or in case of premature study discontinuation, at the early withdrawal visit) and were based on a single serum sample taken in fasting conditions, prior to IMP administration. Percentage of subjects with a normalised (age and sex adjusted) IGF-1 level at the end of the co-administration period, summarised by previous treatment and by final pegvisomant dose are presented. The denominator used to calculate percentages was the number of subjects in each subgroup, comprising previous treatment with pegvisomant, lanreotide Autogel and octreotide long acting repeatable (LAR) and final pegvisomant dose as either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week. The LOCF approach was used to replace missing IGF-1 values.
次要结局
- Percentage of Subjects With Normalised (Age and Sex Adjusted) IGF-1 at Each Assessment(V1 (Screening) up to V11 (Week 44))
- Change From Baseline in Serum IGF-1 Levels (Expressed as Z-scores) During the Co-administration Period(V3 (Week 12; Baseline) up to V11 (Week 44))
- Percentage of Subjects With a Normalised (Age and Sex Adjusted) IGF-1 Level at Any Time During the Co-administration Period(V3 (Week 12; Baseline) up to V11 (Week 44))
- Change From Baseline in Acromegaly Symptoms During the Co-administration Period(V3 (Week 12; Baseline) up to V11 (Week 44))
- Correlation Between the Changes in ACROQoL Assessments With the Corresponding Changes in Z-score of IGF-1 Levels Over the Run-in Period and Co-administration Period(At V2 (Day 1; Run-in), V3 (Week 12; Baseline) and V11 (Week 44))
- Change From Baseline in Mean Supine Systolic and Diastolic Blood Pressure (BP) During the Co-administration Period(V3 (Week 12; Baseline) up to V11 (Week 44))
- Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate During the Co-administration Period(V3 (Week 12; Baseline) up to V11 (Week 44))
- Number of Subjects With Shift in Presence/Absence of Lithiasis and/or Sludge During Co-administration Period(V3 (Week 12; Baseline) up to V11 (Week 44))
- Change From Baseline in Mean Glycosylated Haemoglobin (HbA1C) During the Co-administration Period; Assessed in Non Diabetic and Diabetic Subjects(V3 (Week 12; Baseline) up to V11 (Week 44))
- Change From Baseline in Acromegaly Quality of Life (ACROQoL) Assessments During the Co-administration Period(V3 (Week 12; Baseline) up to V11 (Week 44))
- Change From Baseline in Mean Weight From Baseline During the Co-administration Period(V3 (Week 12; Baseline) up to V11 (Week 44))
- Change From Baseline in Mean Supine Heart Rate During the Co-administration Period(V3 (Week 12; Baseline) up to V11 (Week 44))
- Change From Baseline in Mean PR Interval, QRS Interval, QT Interval, RR Interval and QTcF During the Co-administration Period(V3 (Week 12; Baseline) up to V11 (Week 44))
- Change From Baseline in Mean Fasting Insulin / Glucose Ratio During the Co-administration Period; Assessed in Non Diabetic Subjects(V3 (Week 12; Baseline) up to V11 (Week 44))
- Change From Baseline in Mean Pituitary Tumour Size During the Co-administration Period(V3 (Week 12; Baseline) up to V11 (Week 44))
- Change From Baseline in Mean Blood Glucose Maximum Concentration (Cmax) From Oral Glucose Tolerance Test (OGTT) During the Co-administration Period; Assessed in Non Diabetic Subjects(V3 (Week 12; Baseline) up to V11 (Week 44))
- Change From Baseline in Mean Fasting Insulin Concentration During the Co-administration Period; Assessed in Non Diabetic Subjects(V3 (Week 12; Baseline) up to V11 (Week 44))
- Change From Baseline in Mean Fasting Glucose Concentration During the Co-administration Period; Assessed in Non Diabetic Subjects(V3 (Week 12; Baseline) up to V11 (Week 44))
- Change From Baseline in Liver Function Test Parameters During the Co-administration Period(V3 (Week 12; Baseline) up to V11 (Week 44))
- Change From Baseline in Total Bilirubin During the Co-administration Period(V3 (Week 12; Baseline) up to V11 (Week 44))
- Change From Baseline in Prothrombin Time (Expressed as a Percentage of Normal) During the Co-administration Period(V3 (Week 12; Baseline) up to V11 (Week 44))
- Number of Subjects With Putative Antibodies to Lanreotide and to Pegvisomant During the Co-administration Period(V3 (Week 12; Baseline) up to V11 (Week 44))