- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT00762190
Study of TAK-559 in Treating Subjects With Type 2 Diabetes Mellitus
A Multicenter, Double-Blind, Placebo-Controlled, Randomized Study of the Safety of TAK-559 in the Treatment of Patients With Type 2 Diabetes Mellitus
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
Insulin is a primary regulator of blood glucose concentrations. A subnormal response to circulating insulin levels at target tissues leads to a decrease in insulin-mediated glucose uptake. Insulin resistance is associated with normal to high insulin levels and is often accompanied by dyslipidemia, a disruption in lipid metabolism resulting in increased triglycerides and low-density lipoprotein levels as well as decreased high-density lipoprotein levels in patients with type 2 diabetes mellitus. In the early stages of insulin resistance, a compensatory mechanism of increased insulin secretion by the pancreas maintains normal to near-normal glucose levels. Once the pancreas fails to maintain the increased insulin output, overt type 2 diabetes mellitus occurs.
Insulin also plays an important role in the metabolism of fat and proteins and exerts its influence at the peroxisome proliferator-activated receptor level. Peroxisome proliferator-activated receptor -alpha receptors are expressed predominantly in skeletal muscle, adipose tissue, heart, liver, kidney, gut, macrophages, and vascular tissue, and play a key role in energy storage, glucose homeostasis, and vascular biology. Thus, as insulin activates peroxisome proliferator-activated receptor-alpha receptors, this results in the cellular uptake of glucose. Peroxisome proliferator-activated receptor receptors are ligand-activated transcription elements that regulate gene expression necessary for metabolism. For this reason, peroxisome proliferator-activated receptors play a pivotal role in glucose homeostasis, adipocyte differentiation, and lipid storage. The genes predominantly targeted by transcription activity of activated peroxisome proliferator-activated receptor-alpha receptors are those that mediate fatty acid uptake, fatty acid oxidation, and lipoprotein metabolism. As such, peroxisome proliferator-activated receptor-alpha agonists have their greatest effect on lipid metabolism and vascular biology.
TAK-559 is a novel oxyiminoalkanoic acid under investigation for use as an oral agent in the treatment of patients with type 2 diabetes mellitus. TAK-559 has partial peroxisome proliferator-activated receptor-alpha agonist activity, potent peroxisome proliferator-activated receptor-alpha activity, and modest peroxisome proliferator-activated receptor-gamma activity at high concentrations in nonclinical models.
This study was designed to evaluate the safety of TAK-559 in the treatment of patients with type 2 diabetes mellitus who were on a stable dose of insulin.
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 3
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
Inclusion Criteria:
- Had type 2 diabetes mellitus using American Diabetes Association diagnostic criteria, currently treated with insulin therapy.
- Required sponsor approval if older than 65 years.
- Had a Screening glycosylated hemoglobin less than or equal to 8.0%.
- Had a Screening fasting plasma glucose less than or equal to 200 mg/dL (11.1 mmol/L).
- Had a Screening low density lipoprotein less than or equal to 160 mg/dL (4.1 mmol/L).
- Had a Screening thyroid stimulating hormone level less than or equal to 5.5 μU/mL (5.5 μU/L) and greater than or equal to 0.35 μU/mL (0.35 μU/L).
- Was willing to continue dietary counseling during study and had dietary advice greater than or equal to 2.5 months prior to Screening.
- Had a Screening ejection fraction greater than or equal to 40% from echocardiogram.
- Had a Screening blood pressure less than or equal to 140/95 mm Hg.
- Was willing to perform daily self-monitoring blood glucose tests.
- A female subject of childbearing potential who was sexually active agreed to use adequate contraception, and was neither pregnant nor lactating from Screening throughout the duration of the study.
- Was in good health as determined by physician (via medical history and physical examination) other than having type 2 diabetes mellitus.
- Had clinical laboratory evaluations within normal reference range or deemed not clinically significant by the investigator or sponsor.
- Started insulin therapy at least 3 months prior to Randomization.
Exclusion Criteria:
- Had a hypersensitivity to peroxisome proliferator-activated receptor -alpha or gamma agonists, thiazolidinediones, or fibrates.
- Was diagnosed with type 1 diabetes mellitus or hemochromatosis, or had a history of ketoacidosis.
- Required greater than 2 hypertension medications to achieve adequate blood pressure control.
- Had a history of coronary angioplasty or bypass graft, or unstable angina pectoris within 1 year of Screening.
- Had a history of myocardial infarction.
- Had a history of transient ischemic attack or documented cerebrovascular accident within 6 months of Screening.
- Abdominal, thoracic, or vascular surgery within 6 months of Screening warranting exclusion (investigator's opinion).
- Had a screening creatine phosphokinase value greater than 3 times the upper limit of normal.
- Had persistent unexplained microscopic or macroscopic hematuria or history of bladder cancer.
- Had a screening triglyceride level greater than 500 mg/dL (5.6 mmol/L).
- Experienced a change in allowed lipid-lowering medication (dose or drug) within 2 months of Randomization.
- Experienced a change in blood pressure medication (dose or drug) within 1 month of Randomization.
- Had systemic corticosteroids within 1 month of Randomization.
- Had donated or received blood products within 3 months of Randomization.
- Had a condition known to invalidate glycosylated hemoglobin.
- Had a history of drug abuse or alcohol abuse within 2 years.
- Had a significant cardiovascular disease, including New York Heart Association Functional (Cardiac) Classification II, III or IV.
- Had a Screening B-Type Natriuretic Peptide greater than 100 pg/mL (100 ng/L).
- Had a history of left ventricular hypertrophy (women greater than 110 g/m2 and men greater than 134 g/m2).
- Had a clinically significant mitral insufficiency at Screening.
- Had a clinically significant aortic stenosis at Screening.
- Had a Screening body mass index greater than 45.
- Had a history of cancer with no remission within 5 years of Randomization, other than basal cell or stage 1 squamous cell carcinoma of the skin.
- Had an alanine transaminase or aspartate transaminase level greater than 3 times the upper limit of normal, active liver disease or jaundice at Screening.
- Had a positive human immunodeficiency virus, hepatitis B surface antigen, or hepatitis B e antigen test at Screening.
Was required to take or intended to continue taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication that may interfered with the evaluation of the study medication, including:
- oral antidiabetic agents (including sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, peroxisome proliferator-activated receptor agonists and metformin)
- fibrates
- systemic corticosteroids
- warfarin
- rifampin
- nicotinic acid
- minoxidil
- hydralazine
- St. John's Wort
- Was participating or had participated in an investigational study within the past 30 days.
- Had a serious disease or condition at Screening or Randomization that could affect life expectancy or made it difficult to manage/follow patient according to protocol.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Vervierfachen
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
---|---|
Aktiver Komparator: Insulin
|
TAK-559 placebo-matching, tablets, orally, once daily and insulin stable dose injection for up to 54 weeks.
|
Experimental: TAK-559 32 mg QD + Insulin
|
TAK-559 32 mg, tablets, orally, once daily and insulin stable dose injection for up to 54 weeks.
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
---|---|
Incidence of Adverse events.
Zeitfenster: All visits or at occurrence.
|
All visits or at occurrence.
|
Clinical safety lab tests.
Zeitfenster: Weeks 12, 24, and Final Visit.
|
Weeks 12, 24, and Final Visit.
|
12-lead electrocardiogram.
Zeitfenster: Weeks: 24 and Final Visit.
|
Weeks: 24 and Final Visit.
|
Urinalysis.
Zeitfenster: Weeks: 12, 24, 36, 48 and Final Visit.
|
Weeks: 12, 24, 36, 48 and Final Visit.
|
Change from Baseline in Blood pressure and pulse.
Zeitfenster: At all visits.
|
At all visits.
|
Change from Baseline in Body weight.
Zeitfenster: At all visits.
|
At all visits.
|
Left ventricular mass index by body surface area measured by echocardiogram.
Zeitfenster: Weeks: 24 and Final Visit.
|
Weeks: 24 and Final Visit.
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
---|---|
Change from Baseline in total daily dose of insulin.
Zeitfenster: At all visits.
|
At all visits.
|
Change from Baseline in triglycerides.
Zeitfenster: Weeks: 24 and Final Visit.
|
Weeks: 24 and Final Visit.
|
Change from Baseline in cholesterol.
Zeitfenster: Weeks 24 and Final Visit
|
Weeks 24 and Final Visit
|
Change from Baseline in total, high-density lipoproteins.
Zeitfenster: Weeks: 24 and Final Visit.
|
Weeks: 24 and Final Visit.
|
Change from Baseline in low-density lipoproteins.
Zeitfenster: Weeks 24 and Final Visit
|
Weeks 24 and Final Visit
|
Change from Baseline in low-density lipoprotein fractionation.
Zeitfenster: Weeks 24 and Final Visit
|
Weeks 24 and Final Visit
|
Change from Baseline in very low-density lipoprotein.
Zeitfenster: Weeks 24 and Final Visit
|
Weeks 24 and Final Visit
|
Change from Baseline in free fatty acids.
Zeitfenster: Weeks 24 and Final Visit
|
Weeks 24 and Final Visit
|
Change from Baseline in apolipoproteins (AI, B).
Zeitfenster: Weeks 24 and Final Visit
|
Weeks 24 and Final Visit
|
Mitarbeiter und Ermittler
Sponsor
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Schätzen)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- 01-03-TL-559-016
- U1111-1128-1034 (Registrierungskennung: WHO)
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .
Klinische Studien zur Diabetes Mellitus
-
Medical College of WisconsinMedical University of South CarolinaAbgeschlossenDiabetes Mellitus | Typ 2 Diabetes mellitus | Altersdiabetes mellitus | Nicht insulinabhängiger Diabetes mellitus | Nicht insulinabhängiger Diabetes Mellitus, Typ IIVereinigte Staaten
-
University of Colorado, DenverMassachusetts General Hospital; Beta Bionics, Inc.AbgeschlossenDiabetes mellitus, Typ 1 | Diabetes Typ 1 | Diabetes Typ1 | Diabetes mellitus Typ 1 | Autoimmundiabetes | Diabetes mellitus, insulinabhängig | Jugenddiabetes | Diabetes, Autoimmun | Insulinabhängiger Diabetes mellitus 1 | Diabetes mellitus, insulinabhängig, 1 | Diabetes mellitus, spröde | Diabetes mellitus... und andere BedingungenVereinigte Staaten
-
SanofiAbgeschlossenDiabetes mellitus Typ 1 – Diabetes mellitus Typ 2Ungarn, Russische Föderation, Deutschland, Polen, Japan, Vereinigte Staaten, Finnland
-
Guang NingRekrutierungTyp 2 Diabetes mellitus | Diabetes mellitus Typ1 | Monogenetischer Diabetes | Pankreatogener Diabetes | Medikamenteninduzierter Diabetes mellitus | Andere Formen von Diabetes mellitusChina
-
Meir Medical CenterAbgeschlossenDiabetes mellitus Typ 2 | Diabetes mellitus, nicht insulinabhängig | Diabetes mellitus, zur oralen hypoglykämischen Behandlung | Diabetes mellitus vom ErwachsenentypIsrael
-
Hanmi Pharmaceutical Company LimitedUnbekanntTyp 2 Diabetes mellitus | Diabetes mellitus Typ1Vereinigte Staaten
-
Joslin Diabetes CenterCambridge Medical Technologies, LLCAbgeschlossenTyp 2 Diabetes mellitus | Diabetes mellitus Typ1Vereinigte Staaten
-
Leiden University Medical CenterAndaluz Health ServiceAbgeschlossenDiabetes Mellitus | Gesundheitsverhalten | Selbstwirksamkeit | Typ 2 Diabetes mellitus | Diabetes mellitus Typ1Niederlande, Spanien
-
Hoffmann-La RocheRoche DiagnosticsAbgeschlossenDiabetes mellitus Typ 2, Diabetes mellitus Typ 1Deutschland
-
University of California, San FranciscoJuvenile Diabetes Research FoundationAbgeschlossenDiabetes mellitus Typ 1 | Diabetes mellitus, Typ I | Insulinabhängiger Diabetes mellitus 1 | Diabetes mellitus, insulinabhängig, 1 | IDDMVereinigte Staaten, Australien
Klinische Studien zur TAK-559 and insulin
-
TakedaBeendet
-
TakedaAbgeschlossen
-
TakedaBeendet
-
Assiut UniversityAbgeschlossen
-
Sun Yat-sen UniversityEli Lilly and Company; Ministry of Health, China; Amylin Pharmaceuticals, LLC.AbgeschlossenDiabetes mellitus, Typ 2 | Neu diagnostiziertChina
-
Second Xiangya Hospital of Central South UniversityThe First Affiliated Hospital with Nanjing Medical University; Beijing Hospital und andere MitarbeiterAbgeschlossenDiabetes mellitus, Typ 1China