Overview of Phase I Trials of 2',3'-Dideoxyinosine (ddI) Conducted on Adult Patients

• Published in: Reviews of infectious diseases 1990-07, Vol.12, p.S570-S575
• Main Authors: Marcel Rozencweig, Colin Mc Laren, Mohan Beltangady, Jitka Ritter, Renzo Canetta, Lee Schacter, Susan Kelley, Claude Nicaise, Laurie Smaldone, Lisa Dunkle, Rashmi Barbhaiya, Cathy Knupp, Cross, Anne, Michael Tsianco, R. Russell Martin
• Format: Article
• Language: English
• Subjects: Acquired Immunodeficiency Syndrome - complications; Acquired Immunodeficiency Syndrome - drug therapy; Administered dose; Adult; AIDS; AIDS related complex; AIDS-Related Complex - complications; AIDS-Related Complex - drug therapy; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antigens; Biological and medical sciences; Didanosine - administration & dosage; Didanosine - adverse effects; Didanosine - therapeutic use; Dosage; Drug Evaluation; Experimentation; Female; HIV; Humans; Hyperuricemia; Male; Medical sciences; Middle Aged; Multicenter Studies as Topic; Opportunistic Infections - complications; Pancreatitis; Pancreatitis - chemically induced; Peripheral Nervous System Diseases - chemically induced; Pharmacology. Drug treatments; Symptoms; Uric Acid - blood
• ISSN: 0162-0886

Ninety-two adult patients with AIDS or severe AIDS-related complex were treated with 2',3'-dideoxyinosine (didanosine; ddI) at dosages ranging from 0.8 to 66.0 mg/(kg·d) for at least 6 weeks in phase I trials. Potentially beneficial changes in weight (40% of patients), clinical signs or symptoms (40% of patients), CD4⁺ cell counts (25% of patients), and serum levels of HIV p24 antigen (50% of antigen-positive patients) were reported. Response rates tended to be higher among patients with AIDS-related complex and among those who had not received prior zidovudine therapy. A major response (improvement in at least one clinical parameter and in at least one laboratory marker) occurred in 29% of patients, and rates of major response tended to be higher in patients receiving higher dosages. The primary dose-limiting toxicity observed was peripheral neuropathy, which was observed with increasing frequency in patients receiving >20 mg/(kg·d). Of the other adverse effects, pancreatitis was possibly dose-dependent and hyperuricemia (without clinical gout) occurred only at high doses. Dosages of 250 mg and 375 mg of ddI twice daily will be used in extended phase II/III studies.