Comparison of pharmacokinetics, pharmacodynamics, safety, and tolerability of the amyloid β monoclonal antibody solanezumab in japanese and white patients with mild to moderate Alzheimer disease

Kazunori Uenaka, Masako Nakano, Brian A. Willis, Stuart Friedrich, Lisa Ferguson-Sells, Robert A. Dean, Ichiro Ieiri, Eric R. Siemers

Research output: Contribution to journalArticle

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Abstract

OBJECTIVES: Solanezumab is a humanized anti-amyloid β monoclonal antibody being developed as a passive immunization treatment to slow the progression of Alzheimer disease (AD). Pharmacokinetics (PK), pharmacodynamics, safety, and tolerability after a single dose of solanezumab were compared between Japanese and white patients with AD. METHODS: Japanese and white patients with mild to moderate AD were enrolled in 2 separate studies. In each study, single doses of solanezumab at 0.5, 1.5, 4.0, and 10.0 mg/kg were administered by intravenous infusion. Plasma concentrations of solanezumab and amyloid β (Aβ) were measured. A safety assessment was conducted up to 112 days after a single-dose administration of solanezumab. RESULTS: The PK profile was similar between the Japanese and the white patients with AD. In both the Japanese and the white patients, clearance and volume of distribution appeared similar across doses, suggesting that solanezumab exhibited dose-proportional PK within the studied dose range. A marked increase in plasma total Aβ was observed; both the magnitude and time to reach maximum concentration tended to increase with increasing doses of solanezumab. Administration of solanezumab was generally well-tolerated in both Japanese and white patients with AD. CONCLUSIONS: When administered as a per-kilogram single dose of solanezumab, PK and pharmacodynamics (plasma total Aβ1-40 concentration) in the Japanese patients with AD were comparable with those in the white patients with AD. In addition, solanezumab was generally well tolerated in both Japanese and white patients at all dose levels.

Original languageEnglish
Pages (from-to)25-29
Number of pages5
JournalClinical Neuropharmacology
Volume35
Issue number1
DOIs
Publication statusPublished - Jan 1 2012

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solanezumab
Amyloid
Alzheimer Disease
Pharmacokinetics
Monoclonal Antibodies
Safety
Passive Immunization

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Clinical Neurology
  • Pharmacology (medical)

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Comparison of pharmacokinetics, pharmacodynamics, safety, and tolerability of the amyloid β monoclonal antibody solanezumab in japanese and white patients with mild to moderate Alzheimer disease. / Uenaka, Kazunori; Nakano, Masako; Willis, Brian A.; Friedrich, Stuart; Ferguson-Sells, Lisa; Dean, Robert A.; Ieiri, Ichiro; Siemers, Eric R.

In: Clinical Neuropharmacology, Vol. 35, No. 1, 01.01.2012, p. 25-29.

Research output: Contribution to journalArticle

Uenaka, Kazunori ; Nakano, Masako ; Willis, Brian A. ; Friedrich, Stuart ; Ferguson-Sells, Lisa ; Dean, Robert A. ; Ieiri, Ichiro ; Siemers, Eric R. / Comparison of pharmacokinetics, pharmacodynamics, safety, and tolerability of the amyloid β monoclonal antibody solanezumab in japanese and white patients with mild to moderate Alzheimer disease. In: Clinical Neuropharmacology. 2012 ; Vol. 35, No. 1. pp. 25-29.
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abstract = "OBJECTIVES: Solanezumab is a humanized anti-amyloid β monoclonal antibody being developed as a passive immunization treatment to slow the progression of Alzheimer disease (AD). Pharmacokinetics (PK), pharmacodynamics, safety, and tolerability after a single dose of solanezumab were compared between Japanese and white patients with AD. METHODS: Japanese and white patients with mild to moderate AD were enrolled in 2 separate studies. In each study, single doses of solanezumab at 0.5, 1.5, 4.0, and 10.0 mg/kg were administered by intravenous infusion. Plasma concentrations of solanezumab and amyloid β (Aβ) were measured. A safety assessment was conducted up to 112 days after a single-dose administration of solanezumab. RESULTS: The PK profile was similar between the Japanese and the white patients with AD. In both the Japanese and the white patients, clearance and volume of distribution appeared similar across doses, suggesting that solanezumab exhibited dose-proportional PK within the studied dose range. A marked increase in plasma total Aβ was observed; both the magnitude and time to reach maximum concentration tended to increase with increasing doses of solanezumab. Administration of solanezumab was generally well-tolerated in both Japanese and white patients with AD. CONCLUSIONS: When administered as a per-kilogram single dose of solanezumab, PK and pharmacodynamics (plasma total Aβ1-40 concentration) in the Japanese patients with AD were comparable with those in the white patients with AD. In addition, solanezumab was generally well tolerated in both Japanese and white patients at all dose levels.",
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AU - Friedrich, Stuart

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N2 - OBJECTIVES: Solanezumab is a humanized anti-amyloid β monoclonal antibody being developed as a passive immunization treatment to slow the progression of Alzheimer disease (AD). Pharmacokinetics (PK), pharmacodynamics, safety, and tolerability after a single dose of solanezumab were compared between Japanese and white patients with AD. METHODS: Japanese and white patients with mild to moderate AD were enrolled in 2 separate studies. In each study, single doses of solanezumab at 0.5, 1.5, 4.0, and 10.0 mg/kg were administered by intravenous infusion. Plasma concentrations of solanezumab and amyloid β (Aβ) were measured. A safety assessment was conducted up to 112 days after a single-dose administration of solanezumab. RESULTS: The PK profile was similar between the Japanese and the white patients with AD. In both the Japanese and the white patients, clearance and volume of distribution appeared similar across doses, suggesting that solanezumab exhibited dose-proportional PK within the studied dose range. A marked increase in plasma total Aβ was observed; both the magnitude and time to reach maximum concentration tended to increase with increasing doses of solanezumab. Administration of solanezumab was generally well-tolerated in both Japanese and white patients with AD. CONCLUSIONS: When administered as a per-kilogram single dose of solanezumab, PK and pharmacodynamics (plasma total Aβ1-40 concentration) in the Japanese patients with AD were comparable with those in the white patients with AD. In addition, solanezumab was generally well tolerated in both Japanese and white patients at all dose levels.

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