Aldafermin (NGM282) for Chronic Diarrhea Due to Bile Acid Malabsorption (BAM)

Exclusion Criteria

• •1. Pregnant or lactating
• •2. Structural or metabolic diseases/conditions that affect the gastrointestinal system
• •3. Use of the following medications at least 14 days prior to Visit 1 throughout the duration of the treatment period
• •* Patients may elect to withdraw from bile acid sequestrants such as colestipol, cholestyramine and colesevelam or they may continue but they must continue at the same dose throughout the study.
• •* GI medications including:
• •* Anti-nausea agents including trimethobenzamide, promethazine, prochlorperazine, dimenhydrinate, hydroxyzine
• •* Osmotic laxative agents including lactulose, sorbitol or PEG solutions as Miralax and Glycolax
• •* Prokinetic agents including tegaserod, metoclopramide, prucalopride, domperidone, erythromycin, clarithromycin and azithromycin.
• •* 5-HT3 antagonists including alosetron, ondansetron, tropisetron
• •* Drugs with a known pharmacological activity at 5-HT4, 5-HT2b or 5-HT3 receptors including tegaserod, ondansetron, granisetron and tropisetron
• •* All narcotics including codeine, morphine, and propoxyphene, either alone or in combination
• •* Anti-cholinergics including dicyclomine, hyoscyamine, propantheline.
• •* Antimuscarinics
• •* Tramadol
• •* Peppermint oil
• •* Systemic antibiotics and antibiotics directed at colonic flora including rifaximin and metronidazole
• •4. Use of CNS stimulant medications, including methylphenidate, atomoxetine, modafinil, amphetamines or phentermine.
• •5. Clinically relevant changes in dietary, lifestyle, or exercise regimen within 30 days prior to Visit 1 Screen and throughout the duration of the study
• •6. Any colonic or major abdominal surgery including bariatric surgery, gastric banding, stomach surgery and intestinal or colonic surgery. Procedures such as appendectomy, cholecystectomy, hysterectomy, caesarean section, or polypectomy are allowed as long as they have occurred at least 3 months prior to Visit 1 Screen.
• •7. .History of colorectal cancer, inflammatory bowel disease, diverticulitis, ischemic colitis, microscopic colitis or celiac disease
• •8. History of organic abnormalities of the GI tract, intestinal obstruction, stricture, toxic megacolon, GI perforation, or impaired intestinal circulation.
• •9. Other GI diseases such as GI bleeding or ulcerations
• •10. History of cerebrovascular disease including stroke, TIA, acute coronary syndrome, myocardial infarction or unstable angina
• •11. Clinically significant cardiac history or presence of electrocardiogram (ECG) findings at Visit 1 Screen:
• •* Abnormal heart rate \< 40 or \> 100 beats per minute
• •* QTc interval \> 470 milliseconds (ms)
• •* QRS interval ≥ 110 ms
• •* PR interval ≥ 220 ms
• •12. Hepatic dysfunction including abnormal serum alanine aminotransferase \[ALT\] or aspartate transaminase \[AST\] \> 3 × upper limit of normal \[ULN\]); total direct bilirubin \> 2 × ULN, or alkaline phosphatase \> 2 × ULN at Visit 1 Screen
• •13. Clinically significant renal insufficiency including serum creatinine \> 2.5 mg/dL at Visit 1 Screen
• •14. History of severe head injury or history of seizures
• •15. History of suicide attempt or a hospitalization for a major psychiatric condition within 1 year prior to Visit 1 Screen. At Visit 1 Screen or during the optional remote consent and eligibility review, participants will complete the Hospital Anxiety and Depression questionnaire. If either score for anxiety or depression individually exceeds 8, the score will be discussed. The patient will be and advised whether to participate or whether to see their primary care physician.
• •16. History of alcohol use disorder or substance use disorder within 2 years of Visit 1 Screen.
• •17. Significant history or clinical manifestation of any endocrine, allergic, dermatological, hepatic, renal, hematological, pulmonary, GI, neurological or psychiatric disorder, malignancy (with the exception of treated basal cell carcinomas), or any other condition that would prevent the individual from participating in the study due to risk to the scientific validity of study assessments or to personal well-being of the patient.
• •18. Participated in another clinical study that includes an investigational drug or a biologic therapy within 30 days or 5 half-lives, whichever time period is longer, prior to Visit 1 Screen.