Overview of phase I trials of 2',3'-dideoxyinosine (ddI) conducted on adult patients.
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 greater than 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.
Rozencweig
M
M
Bristol-Myers Squibb Company, Pharmaceutical Research and Development Division, Wallingford, Connecticut 06492-7660.
McLaren
C
C
Beltangady
M
M
Ritter
J
J
Canetta
R
R
Schacter
L
L
Kelley
S
S
Nicaise
C
C
Smaldone
L
L
Dunkle
L
L
D000386:AIDS-Related Complex / Q000150:complications / Q000188:drug therapy*; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy*; D000328:Adult; D016049:Didanosine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009894:Opportunistic Infections / Q000150:complications; D010195:Pancreatitis / Q000139:chemically induced; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D014527:Uric Acid / Q000097:blood
D014527:Uric Acid; D016049:Didanosine