Efficacy and Safety of Lixisenatide in Patients With Type 2 Diabetes Mellitus Insufficiently Controlled by Metformin (GetGoal-M-Asia)
2016年8月18日 更新者：Sanofi
Efficacy and Safety of Lixisenatide in Patients With Type 2 Diabetes Mellitus Insufficiently Controlled by Metformin (With or Without Sulfonylurea): a Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study With 24-week Treatment Period
The purpose of this study is to evaluate the benefits and risks of lixisenatide (AVE0010) in comparison to placebo, as an add-on treatment to metformin with or without sulfonylurea, over a period of 24 weeks of treatment.
The primary objective is to assess the effects on glycemic control of lixisenatide (AVE0010) in comparison to placebo as an add-on treatment to metformin with or without sulfonylurea in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 24.
The secondary objectives are to assess the effects of lixisenatide over 24 weeks on percentage of patients reaching HbA1c less than (< ) 7 percent (%) or HbA1c less than or equal to (<=) 6.5%, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (PPG) and glucose excursion during standardized meal test, body weight; to evaluate safety, tolerability, pharmacokinetic (PK) and anti-lixisenatide antibody development.
調査の概要
詳細な説明
The study duration for each patient is 27 weeks +/- 10 days (up to 2 weeks screening + 1 week run-in + 24 weeks double-blind treatment + 3 days follow-up).
研究の種類
介入
入学 (実際)
391
段階
- フェーズ 3
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Bangkok、タイ、10400
- Investigational Site Number 764002
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Kelantan、マレーシア、16150
- Investigational Site Number 458001
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Kuala Lumpur、マレーシア、59100
- Investigational Site Number 458003
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Putrajaya、マレーシア、62250
- Investigational Site Number 458002
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Beijing、中国、100034
- Investigational Site Number 156011
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Beijing、中国、100101
- Investigational Site Number 156012
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Beijing、中国、100191
- Investigational Site Number 156019
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Beijing、中国、100700
- Investigational Site Number 156002
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Beijing、中国、100730
- Investigational Site Number 156003
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Beijing、中国、100730
- Investigational Site Number 156009
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Beijing、中国、100853
- Investigational Site Number 156001
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Changchun、中国、130041
- Investigational Site Number 156036
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Changsha、中国、410008
- Investigational Site Number 156016
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Changsha、中国、410011
- Investigational Site Number 156015
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Chengdu、中国、610041
- Investigational Site Number 156006
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Chengdu、中国、610072
- Investigational Site Number 156032
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Dalian、中国、116027
- Investigational Site Number 156010
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Guangzhou、中国、510080
- Investigational Site Number 156004
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Guangzhou、中国、510080
- Investigational Site Number 156008
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Guangzhou、中国、510630
- Investigational Site Number 156025
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Haikou、中国、57028
- Investigational Site Number 156031
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Harbin、中国、150001
- Investigational Site Number 156014
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Hefei、中国、230022
- Investigational Site Number 156029
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Qingdao、中国、266003
- Investigational Site Number 156013
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Shanghai、中国、200003
- Investigational Site Number 156007
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Shanghai、中国、200065
- Investigational Site Number 156030
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Shenyang、中国、110004
- Investigational Site Number 156020
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Suzhou、中国、215004
- Investigational Site Number 156035
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Taiyuan、中国、030001
- Investigational Site Number 156033
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Tianjin、中国、300052
- Investigational Site Number 156037
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Xi'An、中国、710032
- Investigational Site Number 156022
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Xi'An、中国、710061
- Investigational Site Number 156023
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Hong Kong、香港
- Investigational Site Number 344001
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Hong Kong、香港
- Investigational Site Number 344003
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Shatin, Nt、香港
- Investigational Site Number 344002
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion criteria:
- Type 2 diabetes mellitus, diagnosed for at least 1 year before screening visit, insufficiently controlled with metformin alone or metformin with sulfonylurea at the time of the screening visit
Exclusion criteria:
- HbA1c <7% or greater than (>) 10% at screening
- At the time of screening age < legal age of majority
- Pregnant or breastfeeding women or women of childbearing potential with no effective contraceptive method
- Type 1 diabetes mellitus
- Treatment with metformin not at a stable dose of at least 1.0 gram per day or more than 1.5 gram per day for at least 3 months prior to screening visit
- In case of treatment with sulfonylurea, if the sulfonylurea dosage is less than the maximum effective dose (that is, half of the maximum recommended dose according to local labeling), or is not at a stable (unchanged) dose for at least 3 months prior to screening
- FPG at screening >250 milligram per deciliter (mg/dL) (>13.9 millimole per liter [mmol/L])
- History of hypoglycemia unawareness
- Body mass index <=20 kilogram per square meter (kg/m^2)
- Weight change of >5 kg during the 3 months preceding the screening visit
- History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, or inflammatory bowel disease or patients considered by the investigator at high risk for acute pancreatitis (for example, with known history of biliary gallstone[s], or with very high triglyceride level [>=5.65 mmol/L]) at the time of screening
- Personal or family history of medullary thyroid cancer or genetic conditions that predispose to medullary thyroid cancer (for example, multiple endocrine neoplasia syndromes);
- History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening
- Hemoglobinopathy or hemolytic anemia, receipt of blood or plasma products within 3 months prior to the time of screening
- Within the last 6 months prior to screening: history of myocardial infarction, stroke, or heart failure requiring hospitalization
- Known history of drug or alcohol abuse within 6 months prior to the time of screening
- Cardiovascular, hepatic, neurological, endocrine disease, active malignant tumor or other major systemic disease or patients with short life expectancy making implementation of the protocol or interpretation of the study results difficult, history or presence of clinically significant diabetic retinopathy, history or presence of macular edema likely to require laser treatment within the study period
- Uncontrolled or inadequately controlled hypertension at the time of screening with a resting systolic blood pressure (SBP) or diastolic blood pressure (DBP) >180 millimeter of mercury (mmHg) or >95 mmHg, respectively
- Laboratory findings at the time of screening: amylase and/or lipase: >3 times upper limit of normal (ULN); hemoglobin <11 gram/deciliter and/or neutrophils <1500 per cubic millimeter (mm^3) and/or platelets <100 000/mm^3; calcitonin >20 picogram per milliliter (5.9 picomole per liter) ; and positive test for Hepatitis B surface antigen and/or Hepatitis C antibody
- Any clinically significant abnormality identified on physical examination, laboratory tests, electrocardiogram, or vital signs at the time of screening that, in the judgment of the investigator or any sub-investigator, precludes safe completion of the study or constrains efficacy assessment
- Patients who are considered by the investigator or any sub-investigator as inappropriate for this study for any reason (for example, impossibility to meet specific protocol requirements, such as attending scheduled visits, being able to do self-injections; likelihood of requiring treatment during the screening phase and treatment phase with drugs not permitted by the clinical study protocol; investigator or any sub-investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol)
- Use of oral or injectable antidiabetic or hypoglycemic agents other than metformin and sulfonylurea (for example, alpha-glucosidase inhibitor, thiazolidinedione, glucagon-like peptide -1 [GLP-1], receptor agonist, dipeptidyl-peptidase-4 inhibitors, insulin) within 3 months prior to the time of screening
- Use of systemic glucocorticoids (excluding topical application or inhaled forms) for 1 week or more within 3 months prior to the time of screening
- Use of any investigational drug within 3 months prior to screening;
- Participation in a previous study with lixisenatide
- Renal impairment defined with creatinine >1.4 mg/dL in women and creatinine >1.5 mg/dL in men
- Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including, but not limited to gastroparesis, unstable (that is, worsening) and not controlled (that is, prolonged nausea and vomiting) gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening
- Allergic reaction to any GLP-1 agonist in the past (for example, exenatide, liraglutide) or to metacresol
- Additional exclusion criteria at the end of the run-in phase: informed consent withdrawal; lack of compliance during the single-blind placebo run-in phase (>2 injections missed); and patient with any adverse event which precludes the inclusion in the study, as assessed by the investigator
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：Lixisenatide
1-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) for 2 weeks, followed by 20 mcg QD up to Week 24.
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1 日 1 回、朝食前の 1 時間以内に皮下注射による自己投与。
他の名前：
Metformin to be continued at stable dose (at least 1.0 gram per day and not more than 1.5 gram per day) up to Week 24.
Sulfonylurea if given at screening, to be continued up to Week 24.
In patients with a screening HbA1c <8% the dose is decreased by 25% to 50% at randomization and then increased up to the screening dose between Week 4 and 12 as per fasting self-monitored plasma glucose (SMPG) values.
In patients with a screening HbA1c >=8%, the dose is not to be changed at randomization.
In any case, after Week 12, sulfonylurea is to be continued at a stable dose.
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プラセボコンパレーター：Placebo
1-step initiation regimen of volume matching placebo: 10 mcg QD for 2 weeks, followed by 20 mcg QD up to Week 24.
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他の名前：
Metformin to be continued at stable dose (at least 1.0 gram per day and not more than 1.5 gram per day) up to Week 24.
Sulfonylurea if given at screening, to be continued up to Week 24.
In patients with a screening HbA1c <8% the dose is decreased by 25% to 50% at randomization and then increased up to the screening dose between Week 4 and 12 as per fasting self-monitored plasma glucose (SMPG) values.
In patients with a screening HbA1c >=8%, the dose is not to be changed at randomization.
In any case, after Week 12, sulfonylurea is to be continued at a stable dose.
1 日 1 回、朝食前の 1 時間以内に皮下注射による自己投与。
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
時間枠：Baseline, Week 24
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Absolute change = HbA1c value at Week 24 minus HbA1c value at baseline.
The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.
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Baseline, Week 24
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
時間枠：Baseline, Week 24
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Change was calculated by subtracting Baseline value from Week 24 value.
The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 1 day after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.
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Baseline, Week 24
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Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 24
時間枠：Baseline, Week 24
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The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal.
Change was calculated by subtracting Baseline value from Week 24 value.
The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
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Baseline, Week 24
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Change From Baseline in Body Weight at Week 24
時間枠：Baseline, Week 24
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Change was calculated by subtracting Baseline value from Week 24 value.
The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.
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Baseline, Week 24
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Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24
時間枠：Week 24
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The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.
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Week 24
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Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24
時間枠：Week 24
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The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.
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Week 24
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Change From Baseline in Glucose Excursion at Week 24
時間枠：Baseline, Week 24
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Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test, before study drug administration.
Change was calculated by subtracting Baseline value from Week 24 value.
The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
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Baseline, Week 24
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Percentage of Patients Requiring Rescue Therapy During Main 24-Week Period
時間枠：Baseline up to Week 24
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Routine fasting self-monitored plasma glucose (SMPG) and central laboratory FPG (and HbA1c after week 12) values were used to determine the requirement of rescue medication.
If fasting SMPG value exceeded the specified limit for 3 consecutive days, the central laboratory FPG (and HbA1c after week 12) were performed.
Threshold values - from baseline to Week 8: fasting SMPG/FPG >250 milligram/deciliter (mg/dL) (13.9 mmol/L), from Week 8 to Week 12: fasting SMPG/FPG >220 mg/dL (12.2 mmol/L), and from Week 12 to Week 24: fasting SMPG/FPG >200 mg/dL (11.1 mmol/L) or HbA1c >8.5%.
For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.
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Baseline up to Week 24
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24
時間枠：Baseline, Week 24
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The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.
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Baseline, Week 24
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症候性低血糖および重度の症候性低血糖の患者数
時間枠：最終投与後3日以内の治験薬の初回投与
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症候性低血糖とは、血糖値が 60 mg/dL (3.3 mmol/L) 未満である低血糖エピソードに起因すると考えられる臨床症状を伴う事象、または炭水化物の経口投与、ブドウ糖の静脈内投与、またはグルカゴン投与後の迅速な回復に関連する事象である。血漿グルコース測定が利用できなかった場合。
重度の症候性低血糖症は、患者が別の人の助けを必要とする症候性低血糖イベントであり、36 mg/dL (2.0 mmol/L) 未満の血漿グルコースレベル、または経口炭水化物、静脈内グルコース、またはグルカゴン投与後の迅速な回復のいずれかに関連していました、血漿グルコース測定が利用できなかった場合。
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最終投与後3日以内の治験薬の初回投与
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- Yu Pan C, Han P, Liu X, Yan S, Feng P, Zhou Z, Lv X, Tian H, Jin Kui Y, Su B, Shang S, Niemoeller E. Lixisenatide treatment improves glycaemic control in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin with or without sulfonylurea: a randomized, double-blind, placebo-controlled, 24-week trial (GetGoal-M-Asia). Diabetes Metab Res Rev. 2014 Nov;30(8):726-35. doi: 10.1002/dmrr.2541.
- Seino H, Onishi Y, Naito Y, Komatsu M. Lixisenatide improves glycemic outcomes of Japanese patients with type 2 diabetes: a meta-analysis. Diabetol Metab Syndr. 2016 Jun 1;8:36. doi: 10.1186/s13098-016-0151-7. eCollection 2016.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2010年7月1日
一次修了 (実際)
2011年12月1日
研究の完了 (実際)
2011年12月1日
試験登録日
最初に提出
2010年7月23日
QC基準を満たした最初の提出物
2010年7月23日
最初の投稿 (見積もり)
2010年7月26日
学習記録の更新
投稿された最後の更新 (見積もり)
2016年10月13日
QC基準を満たした最後の更新が送信されました
2016年8月18日
最終確認日
2016年8月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。