The safety and efficacy of combination N-butyl-deoxynojirimycin (SC- 48334) and zidovudine in patients with HIV-1 infection and 200-500 CD4 cells/mm3

Margaret A Fischl, L. Resnick, R. Coombs, A. B. Kremer, J. C. Pottage, R. J. Fass, K. H. Fife, W. G. Powderly, A. C. Collier, R. L. Aspinall, S. L. Smith, K. G. Kowalski, C. B. Wallemark

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

We conducted a double-blind, randomized phase II study to evaluate the safety and activity of combination therapy with N-butyl-deoxynojirimycin (SC- 48334) (an α-glucosidase I inhibitor) and zidovudine versus zidovudine alone. Patients with 200 to 500 CD4 cells/mm3 who tolerated ≤ 12 weeks of prior zidovudine therapy received SC-48334 (1000 mg every 8 h) and zidovudine (100 mg every 8 h) or zidovudine and placebo. Sixty patients received combination therapy and 58, zidovudine and placebo. Twenty-three patients (38%) and 15 (26%), in the combination and zidovudine groups, respectively, discontinued therapy (p = 0.15). The mean SC-48334 steady-state trough level (4.04 ± 0.99 μg/ml) was below the in vitro inhibitory concentration for human immunodeficiency virus (HIV). The mean increase in CD4 cells at week 4 was 73.8 cells/mm3 and 52.4 cells/mm3 for the combination and zidovudine groups, respectively (p > 0.36). For patients with prior zidovudine therapy, the mean change in CD4 cells in the combination and zidovudine groups was 63.7 cells/mm3 and 4.9 cells/mm3 at week 8 and 6.8 cells/mm3 and -45.1 cells/mm3 at week 16, respectively. The number of patients with suppression of HIV p24 antigenemia in the combination and zidovudine groups was six (40%) and two (11%) at week 4 (p = 0.10) and five (45%) and two (14%) at week 24 (p = 0.08), respectively. Diarrhea, flatulence, abdominal pain, and weight loss were common for combination recipients. Although superiority of combination therapy was not seen, these data suggest that SC-48334 has anti-HIV activity and provide a rationale for the evaluation of better tolerated compounds of this class.

Original languageEnglish
Pages (from-to)139-147
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Volume7
Issue number2
StatePublished - Feb 18 1994
Externally publishedYes

Fingerprint

Zidovudine
Virus Diseases
HIV-1
Safety
HIV
miglustat
Therapeutics
Placebos
Flatulence
Abdominal Pain
Weight Loss
Diarrhea

Keywords

  • Combination therapy
  • Glucosidase inhibitor
  • HIV
  • N-Butyl-deoxynojirimycin (SC-48334)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Virology

Cite this

The safety and efficacy of combination N-butyl-deoxynojirimycin (SC- 48334) and zidovudine in patients with HIV-1 infection and 200-500 CD4 cells/mm3 . / Fischl, Margaret A; Resnick, L.; Coombs, R.; Kremer, A. B.; Pottage, J. C.; Fass, R. J.; Fife, K. H.; Powderly, W. G.; Collier, A. C.; Aspinall, R. L.; Smith, S. L.; Kowalski, K. G.; Wallemark, C. B.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 7, No. 2, 18.02.1994, p. 139-147.

Research output: Contribution to journalArticle

Fischl, MA, Resnick, L, Coombs, R, Kremer, AB, Pottage, JC, Fass, RJ, Fife, KH, Powderly, WG, Collier, AC, Aspinall, RL, Smith, SL, Kowalski, KG & Wallemark, CB 1994, 'The safety and efficacy of combination N-butyl-deoxynojirimycin (SC- 48334) and zidovudine in patients with HIV-1 infection and 200-500 CD4 cells/mm3 ', Journal of Acquired Immune Deficiency Syndromes, vol. 7, no. 2, pp. 139-147.
Fischl, Margaret A ; Resnick, L. ; Coombs, R. ; Kremer, A. B. ; Pottage, J. C. ; Fass, R. J. ; Fife, K. H. ; Powderly, W. G. ; Collier, A. C. ; Aspinall, R. L. ; Smith, S. L. ; Kowalski, K. G. ; Wallemark, C. B. / The safety and efficacy of combination N-butyl-deoxynojirimycin (SC- 48334) and zidovudine in patients with HIV-1 infection and 200-500 CD4 cells/mm3 In: Journal of Acquired Immune Deficiency Syndromes. 1994 ; Vol. 7, No. 2. pp. 139-147.
@article{7484fdc1157d48cdb9c9a731c2002b3d,
title = "The safety and efficacy of combination N-butyl-deoxynojirimycin (SC- 48334) and zidovudine in patients with HIV-1 infection and 200-500 CD4 cells/mm3",
abstract = "We conducted a double-blind, randomized phase II study to evaluate the safety and activity of combination therapy with N-butyl-deoxynojirimycin (SC- 48334) (an α-glucosidase I inhibitor) and zidovudine versus zidovudine alone. Patients with 200 to 500 CD4 cells/mm3 who tolerated ≤ 12 weeks of prior zidovudine therapy received SC-48334 (1000 mg every 8 h) and zidovudine (100 mg every 8 h) or zidovudine and placebo. Sixty patients received combination therapy and 58, zidovudine and placebo. Twenty-three patients (38{\%}) and 15 (26{\%}), in the combination and zidovudine groups, respectively, discontinued therapy (p = 0.15). The mean SC-48334 steady-state trough level (4.04 ± 0.99 μg/ml) was below the in vitro inhibitory concentration for human immunodeficiency virus (HIV). The mean increase in CD4 cells at week 4 was 73.8 cells/mm3 and 52.4 cells/mm3 for the combination and zidovudine groups, respectively (p > 0.36). For patients with prior zidovudine therapy, the mean change in CD4 cells in the combination and zidovudine groups was 63.7 cells/mm3 and 4.9 cells/mm3 at week 8 and 6.8 cells/mm3 and -45.1 cells/mm3 at week 16, respectively. The number of patients with suppression of HIV p24 antigenemia in the combination and zidovudine groups was six (40{\%}) and two (11{\%}) at week 4 (p = 0.10) and five (45{\%}) and two (14{\%}) at week 24 (p = 0.08), respectively. Diarrhea, flatulence, abdominal pain, and weight loss were common for combination recipients. Although superiority of combination therapy was not seen, these data suggest that SC-48334 has anti-HIV activity and provide a rationale for the evaluation of better tolerated compounds of this class.",
keywords = "Combination therapy, Glucosidase inhibitor, HIV, N-Butyl-deoxynojirimycin (SC-48334)",
author = "Fischl, {Margaret A} and L. Resnick and R. Coombs and Kremer, {A. B.} and Pottage, {J. C.} and Fass, {R. J.} and Fife, {K. H.} and Powderly, {W. G.} and Collier, {A. C.} and Aspinall, {R. L.} and Smith, {S. L.} and Kowalski, {K. G.} and Wallemark, {C. B.}",
year = "1994",
month = "2",
day = "18",
language = "English",
volume = "7",
pages = "139--147",
journal = "Journal of acquired immune deficiency syndromes (1999)",
issn = "1525-4135",
publisher = "Lippincott Williams and Wilkins Ltd.",
number = "2",

}

TY - JOUR

T1 - The safety and efficacy of combination N-butyl-deoxynojirimycin (SC- 48334) and zidovudine in patients with HIV-1 infection and 200-500 CD4 cells/mm3

AU - Fischl, Margaret A

AU - Resnick, L.

AU - Coombs, R.

AU - Kremer, A. B.

AU - Pottage, J. C.

AU - Fass, R. J.

AU - Fife, K. H.

AU - Powderly, W. G.

AU - Collier, A. C.

AU - Aspinall, R. L.

AU - Smith, S. L.

AU - Kowalski, K. G.

AU - Wallemark, C. B.

PY - 1994/2/18

Y1 - 1994/2/18

N2 - We conducted a double-blind, randomized phase II study to evaluate the safety and activity of combination therapy with N-butyl-deoxynojirimycin (SC- 48334) (an α-glucosidase I inhibitor) and zidovudine versus zidovudine alone. Patients with 200 to 500 CD4 cells/mm3 who tolerated ≤ 12 weeks of prior zidovudine therapy received SC-48334 (1000 mg every 8 h) and zidovudine (100 mg every 8 h) or zidovudine and placebo. Sixty patients received combination therapy and 58, zidovudine and placebo. Twenty-three patients (38%) and 15 (26%), in the combination and zidovudine groups, respectively, discontinued therapy (p = 0.15). The mean SC-48334 steady-state trough level (4.04 ± 0.99 μg/ml) was below the in vitro inhibitory concentration for human immunodeficiency virus (HIV). The mean increase in CD4 cells at week 4 was 73.8 cells/mm3 and 52.4 cells/mm3 for the combination and zidovudine groups, respectively (p > 0.36). For patients with prior zidovudine therapy, the mean change in CD4 cells in the combination and zidovudine groups was 63.7 cells/mm3 and 4.9 cells/mm3 at week 8 and 6.8 cells/mm3 and -45.1 cells/mm3 at week 16, respectively. The number of patients with suppression of HIV p24 antigenemia in the combination and zidovudine groups was six (40%) and two (11%) at week 4 (p = 0.10) and five (45%) and two (14%) at week 24 (p = 0.08), respectively. Diarrhea, flatulence, abdominal pain, and weight loss were common for combination recipients. Although superiority of combination therapy was not seen, these data suggest that SC-48334 has anti-HIV activity and provide a rationale for the evaluation of better tolerated compounds of this class.

AB - We conducted a double-blind, randomized phase II study to evaluate the safety and activity of combination therapy with N-butyl-deoxynojirimycin (SC- 48334) (an α-glucosidase I inhibitor) and zidovudine versus zidovudine alone. Patients with 200 to 500 CD4 cells/mm3 who tolerated ≤ 12 weeks of prior zidovudine therapy received SC-48334 (1000 mg every 8 h) and zidovudine (100 mg every 8 h) or zidovudine and placebo. Sixty patients received combination therapy and 58, zidovudine and placebo. Twenty-three patients (38%) and 15 (26%), in the combination and zidovudine groups, respectively, discontinued therapy (p = 0.15). The mean SC-48334 steady-state trough level (4.04 ± 0.99 μg/ml) was below the in vitro inhibitory concentration for human immunodeficiency virus (HIV). The mean increase in CD4 cells at week 4 was 73.8 cells/mm3 and 52.4 cells/mm3 for the combination and zidovudine groups, respectively (p > 0.36). For patients with prior zidovudine therapy, the mean change in CD4 cells in the combination and zidovudine groups was 63.7 cells/mm3 and 4.9 cells/mm3 at week 8 and 6.8 cells/mm3 and -45.1 cells/mm3 at week 16, respectively. The number of patients with suppression of HIV p24 antigenemia in the combination and zidovudine groups was six (40%) and two (11%) at week 4 (p = 0.10) and five (45%) and two (14%) at week 24 (p = 0.08), respectively. Diarrhea, flatulence, abdominal pain, and weight loss were common for combination recipients. Although superiority of combination therapy was not seen, these data suggest that SC-48334 has anti-HIV activity and provide a rationale for the evaluation of better tolerated compounds of this class.

KW - Combination therapy

KW - Glucosidase inhibitor

KW - HIV

KW - N-Butyl-deoxynojirimycin (SC-48334)

UR - http://www.scopus.com/inward/record.url?scp=0028088988&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028088988&partnerID=8YFLogxK

M3 - Article

VL - 7

SP - 139

EP - 147

JO - Journal of acquired immune deficiency syndromes (1999)

JF - Journal of acquired immune deficiency syndromes (1999)

SN - 1525-4135

IS - 2

ER -