| Inclusion criteria |
Signed written informed consent
Target population
Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination, electrocardiograms, and clinical laboratory determinations Body mass index 18–35 kg/m2 (CV181033), 18–32 kg/m2 (CV181053), and 18–30 kg/m2 (CV181005), inclusive
Age and gender
Men and women who were not of childbearing potential (ie, who were postmenopausal or surgically sterile), 18–45 years of age Women were considered surgically sterile only if they had undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy Women were considered postmenopausal only if they had amenorrhea for ≥12 consecutive months, or for women on hormone replacement therapy, if they had a documented serum follicle-stimulating hormone level >35 mIU/mL
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| Exclusion criteria |
Gender and reproductive status
Women of childbearing potential included any female who had experienced menarche and who had not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or was not postmenopausal as defined in inclusion criteria. Even women who were using oral, implanted, or injectable contraceptive hormones, or mechanical products, such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence, or whose partner was sterile (eg, vasectomy) were considered to be of childbearing potential Women who were pregnant or breastfeeding Women with a positive pregnancy test on enrollment or prior to study drug administration Sexually active fertile men not using effective birth control if their partners were women of childbearing potential (CV181053 only)
Medical history and concurrent diseases
Any significant acute or chronic medical illness Current or recent (within three months) gastrointestinal disease Any major surgery within four weeks of enrollment Any gastrointestinal surgery that could have impacted upon the absorption of study drug Any history of rhabdomyolysis (CV181033) Donation of blood or plasma to a blood bank or in a clinical study (except a screening visit) within four weeks of enrollment Blood transfusion within four weeks of enrollment Inability to tolerate oral medication Inability to be venipunctured and/or tolerate venous access Recent (within six months) drug or alcohol abuse as defined in DSM-IV, Diagnostic Criteria for Drug and Alcohol Abuse Any other sound medical, psychiatric, and/or social reason as determined by the investigator History of low blood pressure or orthostatic hypotension (CV181053) Any current or previous history of nicotine use for at least one year prior to dosing (CV181053)
Physical and laboratory test findings
Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, electrocardiogram, or clinical laboratory determinations. A clinically significant laboratory abnormality is defined as a value >1.25 × upper limit of normal and < 0.85 × lower limit of normal when low values are clinically significant, eg, calcium Positive urine screen for drugs of abuse either at screening or before dosing Positive blood screen for hepatitis C antibody History or evidence on screening of clinically significant arrhythmias, including but not limited to atrioventricular block, sick sinus syndrome, Wolff-Parkinson-White syndrome, and sinus bradycardia (heart rate <55 beats per minute) (CV181053) Heart rate <55 beats per minute based on screening and day 1 predose evaluations (CV181053) Blood pressure <100/60 mmHg based on screening and day 1 predose evaluations (CV181053)
Allergies and adverse drug reactions
History of allergy to DPP-4 inhibitors, HMG-CoA reductase inhibitors (CV181033 only), diltiazem extended-release (CV181053 only), ketoconazole (CV181005 only), or related compounds History of any significant drug allergy
Prohibited therapies and/or medications
Prior exposure to saxagliptin Exposure to any investigational drug or placebo within four weeks of enrollment Use of any prescription drugs or over-the-counter acid controllers within four weeks prior to enrollment Use of any other drugs, including over-the-counter medications and herbal preparations, within one week prior to enrollment Use of an oral, injectable, or implantable hormonal contraceptive agent within three months of enrollment
Other exclusion criteria
Prisoners or subjects who were compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious disease) illness Subjects who smoked (CV181005) or who had smoked in the 30 days prior to screening (CV181033)
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