Resumen

This study will evaluate the longer-term glycemic effect of two medicines approved for initial treatment of type 2 diabetes. The study consists of a 2 week screening period (2 study visits), followed by an 80 week double-blind treatment period (11 study visits). Also, a sub-study was included to look at changes in bone mineral density (BMD) at the lumbar spine.

Descripción detallada

This was a phase IV, randomized, double-blind, global, multi-centre study. The study consisted of a 2 week screening period followed by an 80 week double-blind treatment period. Subjects who met all eligibility requirements were randomized in a 1:1 ratio, stratified by country, gender (male and female) and pre-screening HbA1c (≤9% or\>9) either to MET or AVM. When the substudy was added, a new randomization was created for the participating centers. Those subjects in the bone sub-study were stratified by country, gender (male, premenopausal female, and postmenopausal female), pre-screening HbA1c (i.e., ≤9%; \>9%), and either to MET or AVM. At randomization, Visit 3 (Week 0), subjects were initiated at Dose Level 1. Treatment with AVM was initiated at a dose of 4 mg/500 mg and titrated up to a maximum total daily dose of AVM 8 mg/2000 mg. Treatment with MET therapy was initiated at a dose of 500 mg and titrated up to a maximum daily dose of 2000mg.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 75 YearsSexo: ALL

Criterios de inclusión

The subject provides written informed consent.
The subject is male or female and 18 to 75 years of age at the time of pre-screening.
The subject has an established clinical diagnosis of type 2 diabetes according to recommended guidelines (e.g., American Diabetes Association, International Diabetes Federation, World Health Organization, Canadian Diabetes Association, or American Association of Clinical Endocrinologists).
The subject is currently treated with diet and exercise, and has not taken more than 2 weeks of an anti-diabetic monotherapy or insulin in the past 6 months.
The subject has a BMI \>25 kg/m2 at pre-screening.
The subject has a Quest HbA1c 7.5% to 10.5% at pre-screening.
The subject has a fasting capillary blood glucose 126 mg/dL (7mmol/L), as measured by the site staff at week 0.
If the subject is a pre-menopausal female of child-bearing potential, she agrees to practice acceptable contraceptive measures (e.g. oral birth control pills, Norplant, Depo-Provera, an intrauterine device (IUD), a diaphragm with spermicide or a condom with spermicide, or abstinence) at least 1 month before screening, during the study, and for 30 days after the last dose of study medication is taken
The subject is able and willing to perform self-monitoring of blood glucose as specified in this protocol.

Criterios de exclusión

The subject has taken an oral anti-diabetic monotherapy or insulin for more than 14 days in the past 6 months.
The subject has presence of clinically significant renal or hepatic disease (serum creatinine 1.5 mg/dL (132.6 mol/L) for males and 1.4 mg/dL (123.8 mol/L) for females): ALT, AST, total bilirubin, or alkaline phosphatase \>2.5 times the upper limit of the normal (ULN) reference range.
The subject has anemia defined by hemoglobin concentration \<11g/dL (110g/L) for males or \<10g/dL (100g/L) for females.
Presence of unstable or severe angina, coronary insufficiency or New York Heart Association (NYHA) class III-IV or any congestive heart failure requiring pharmacologic treatment.
The subject has systolic blood pressure \>160 mmHg or diastolic blood pressure \>90 mmHg
The subject has a chronic disease requiring intermittent or chronic treatment with oral, intravenous, or intra-articular corticosteroids (i.e., only use of topical, inhaled or nasal corticosteroids is permitted).
The subject has acute or chronic metabolic acidosis or a history of diabetic ketoacidosis.
The subject has a clinically significant abnormality which in the judgment of the investigator makes the subject unsuitable for inclusion in the study (e.g., physical examination, laboratory tests, or electrocardiogram, etc).
The subject has used an investigational agent within 30 days or 5 half-lives (whichever was longer) prior to pre-screening.
The subject is a female who is lactating, pregnant, or planned to become pregnant.
The subject has a prior history of severe edema or a medically serious fluid related event (e.g., heart failure).
The subject has a history of macular edema.
The subject has significant hypersensitivity (e.g., difficulty swallowing, difficulty breathing, and tachycardia or skin reaction) to TZDs, biguanides, or compounds with similar chemical structures.
The subject has a diagnosis of cancer (other than squamous, basal cell, or cervical cancer in-situ) in the past 3 years and is receiving treatment for cancer.
The subject has a history or suspicion of drug abuse or alcohol abuse within the last 6 months.
The subject is known to have severe lactose intolerance.
The subject is not willing to comply with visits and procedures described in the protocol.
The subject has a disease that may affect bone turnover including, but not limited to: Paget's disease, hypercalcemia, hypocalcemia, hyperparathyroidism, hyperthyroidism, osteomalacia, metastatic bone disease
The subject has a weight of greater than 300 lbs (136.4 kg).
The subject has received treatment with bisphosphonates (≥1 month cumulative treatment within the last 12 months) or fluoride (dose greater than 10mg/day within the previous 5 years).

Intervenciones

drug

Avandamet 6 mg/1500 mg (ttd)

One 2 mg/ 500 mg capsule will be taken in the AM with the morning meal Two 2 mg/ 500 mg capsules will be taken in the PM with the evening meal

drug

Avandamet 4 mg/1000 mg (ttd)

One 2 mg/500 mg capsule will be taken in the AM with the morning meal. One 2 mg/500 mg capsule will be taken in the PM with the evening meal.

drug

Avandamet 2 mg/500 mg (ttd)

one placebo capsule will be taken in the AM with the morning meal one 2 mg/ 500 mg capsule will be taken in the PM with the evening meal.

drug

Avandamet 8 mg/ 2000 mg (ttd)

Two 2 mg/ 500 mg capsules will be taken in the AM with the morning meal. Two 2 mg/ 500 mg capsules will be taken in the PM with the evening meal.

drug

Metformin 500 mg (ttd)

One placebo capsule will be taken in the AM with the morning meal. One 500 mg capsule will be taken in the PM with the evening meal.

drug

Metformin 1000 mg (ttd)

One 500 mg capsule will be taken in the AM with the morning meal. One 500 mg capsule will be taken in the PM with the evening meal.

drug

Metformin 1500 mg (ttd)

One 500 mg capsule will be taken in the AM with the morning meal. Two 500 mg capsules will be taken in the PM with the evening meal.

drug

Metformin 2000 mg (ttd)

Two 500 mg capsule will be taken in the AM with the morning meal. Two 500 mg capsule will be taken in the PM with the evening meal.

Ubicaciones

GSK Investigational Site

Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Buenos Aries, Buenos Aires, Argentina

GSK Investigational Site

Capital Federal, Buenos Aires, Argentina

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Córdoba, Córdoba Province, Argentina

GSK Investigational Site

Mendoza, Mendoza Province, Argentina

GSK Investigational Site

Buenos Aires, Argentina

A Randomized, Parallel Group, Double-blind, Multi-center Study Comparing the Efficacy and Safety of AVANDAMET and Metformin After 80 Weeks of Treatment.

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Avandamet 6 mg/1500 mg (ttd)

Avandamet 4 mg/1000 mg (ttd)

Avandamet 2 mg/500 mg (ttd)

Avandamet 8 mg/ 2000 mg (ttd)

Metformin 500 mg (ttd)

Metformin 1000 mg (ttd)

Metformin 1500 mg (ttd)

Metformin 2000 mg (ttd)

Ubicaciones

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

Patrocinadores