A Phase 1a/1b Study of CB4211 in Healthy Non-obese Subjects and Subjects With Nonalcoholic Fatty Liver Disease

Exclusion Criteria

• •1. Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee).
• •2. Clinically significant ECG abnormalities or QT interval corrected for heart rate using Fridericia's method (QTcF) \>450 milliseconds for males and \>470 milliseconds for females at either Screening or Check-in, or any prior history of QT abnormality.
• •3. Creatinine clearance of \<90 mL/min at Screening, determined using the Cockcroft-Gault (C-G) equation.
• •4. History of febrile illness within 7 days prior to the first dose of study drug or subjects with evidence of active infection.
• •5. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
• •6. History of alcoholism or drug/chemical abuse within 2 years prior to Check-in.
• •7. Alcohol consumption of \>21 units per week for males and \>14 units for females. One unit of alcohol equals 12 oz (360 mL) beer, 1½ oz (45 mL) liquor, or 5 oz (150 mL) wine.
• •8. Positive urine drug screen (confirmed by repeat) at Screening or positive alcohol breath or urine test result or positive urine drug screen at Check-in.
• •9. Positive hepatitis panel and/or positive human immunodeficiency virus test. Subjects with serologic finding of immunity consistent with history of prior hepatitis B vaccination may be enrolled.
• •10. Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days prior to dosing or have received a biological product within 3 months or 5 elimination half-lives (whichever is longer) prior to dosing.
• •11. Use of prescription drugs, nonprescription drugs, dietary supplements including Vitamin E, herbal supplements, hormonal therapy/replacement, or CYP3A4 substrates, inducers and inhibitors within 14 days prior to the first dose of study drug unless, in the opinion of the Investigator and Sponsor's Medical Monitor, the medication will not interfere with the study procedures or compromise subject safety.
• •12. Use or intend to use slow-release medications/products considered to still be active within 14 days prior to Check-in, unless deemed acceptable by the Investigator (or designee).
• •13. Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations within 14 days prior to the first dose of study medication, unless deemed acceptable by the Investigator (or designee).
• •14. Use of tobacco- or nicotine-containing products within 3 months prior to Check-in.
• •15. Receipt of blood products within 2 months prior to Check-in.
• •16. Donation of blood from 56 days prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.
• •17. Poor peripheral venous access.
• •18. Have previously completed or withdrawn from this study or any other study investigating CB4211, and have previously received the investigational product.
• •19. Subjects who, in the opinion of the Investigator (or designee), should not participate in this study.
• •1. Significant history or clinical manifestation of any metabolic/endocrine (except for type 2 diabetes), allergic, dermatological, hepatic (except for NAFLD), renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, or psychiatric disorder, as determined by the Investigator (or designee).
• •2. Clinically significant ECG abnormalities or QTcF \>450 milliseconds for males and 470 milliseconds for females at Screening, or any prior history of QT abnormality.
• •3. Currently using any antidiabetic medication (eg, insulin, glucagon-like peptide-1 analogs, agonist therapy) other than a stable regimen of metformin (ie, a fixed dose of metformin for \>8 weeks at Screening).
• •4. Use of fibrates or statins within 6 weeks or beta blocker drugs within 2 weeks prior to Check-in and throughout the duration of the study.
• •5. Use of Vitamin E, agents associated with changes in liver fat, or agents used for treatment of NAFLD or nonalcoholic steatohepatitis (NASH) within 3 months prior to Screening and throughout the duration of the study.
• •6. Change in body weight \>5% within the 3 months prior to Check-in.
• •7. History of bariatric surgery and any other gastrointestinal surgery relative to weight loss (eg, Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, sleeve gastrectomy, duodenal switch with biliopancreatic diversion).
• •8. Claustrophobia or other contraindication to magnetic resonance imaging.
• •9. Creatinine clearance of \<90 mL/min at Screening, determined using the C-G equation.
• •10. History of febrile illness within 7 days prior to the first dose of study drug or subjects with evidence of active infection.
• •11. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
• •12. History of alcoholism or drug/chemical abuse within 2 years prior to Check-in.
• •13. Alcohol consumption of \>14 units per week for males and \>7 units for females. One unit of alcohol equals 12 oz (360 mL) beer, 1½ oz (45 mL) liquor, or 5 oz (150 mL) wine.
• •14. Positive urine drug screen (confirmed by repeat) at Screening or positive alcohol breath or urine test result or positive urine drug screen at Check-in.
• •15. Positive hepatitis panel and/or positive human immunodeficiency virus test. Subjects with serologic finding of immunity consistent with history of prior hepatitis B vaccination may be enrolled.
• •16. Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days prior to dosing or have received a biological product within 3 months or 5 elimination half-lives (whichever is longer) prior to dosing.
• •17. Use of prescription drugs, nonprescription drugs, dietary supplements including peroxisome proliferator-activated receptor-γ agonists, drugs known to affect insulin sensitivity, herbal supplements, hormonal therapy/replacement, or CYP3A4 substrates, inducers, and inhibitors within 14 days or 5 elimination half-lives (whichever is longer) prior to the first dose of study drug and throughout the duration of the study unless, in the opinion of the Investigator and Sponsor's Medical Monitor, the medication will not interfere with the study procedures or compromise subject safety.
• •18. Use or intend to use slow-release medications/products considered to still be active within 14 days prior to Check-in, unless deemed acceptable by the Investigator (or designee).
• •19. Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations within 14 days prior to the first dose of study medication and throughout the duration of the study, unless deemed acceptable by the Investigator (or designee).
• •20. Use of tobacco- or nicotine-containing products within 3 months prior to Check-in and throughout the duration of the study.
• •21. Receipt of blood products within 2 months prior to Check-in and throughout the duration of the study.
• •22. Donation of blood from 56 days prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.
• •23. Poor peripheral venous access.
• •24. Have previously completed or withdrawn from this study or any other study investigating CB4211, and have previously received the investigational product.
• •25. Subjects who, in the opinion of the Investigator (or designee), should not participate in this study.