Randomized, placebo-controlled trial of trimethobenzamide to control nausea and vomiting during initiation and continued treatment with subcutaneous apomorphine injection

Parkinsonism Relat Disord. 2014 Nov;20(11):1171-6. doi: 10.1016/j.parkreldis.2014.08.010. Epub 2014 Aug 27.

Abstract

Background: Nausea and vomiting can occur in Parkinson's disease (PD) patients initiated on apomorphine subcutaneous injections and antiemetic prophylaxis is recommended per product labeling. Data suggest long-term antiemetic prophylaxis may not be needed, although this has not been systematically studied.

Methods: We evaluated coadministered trimethobenzamide with apomorphine in 182 PD subjects using a randomized, double-blind, placebo-controlled design, with phased withdrawal of subjects from trimethobenzamide to placebo. Evaluations included presence/absence of nausea and vomiting; Index of Nausea, Vomiting, and Retching (INVR); subject evaluation of medication; Unified Parkinson's Disease Rating Scale (UPDRS) motor score; "on" response post-injection; and safety assessments.

Results: Incidence of nausea and/or vomiting on Day 1 of apomorphine initiation (primary endpoint) was not significantly different between trimethobenzamide and placebo. Over a longer period, a significantly lower incidence was found for trimethobenzamide during Period 1 (Days 1-28, p = 0.025) and Period 2 (Days 29-56, p = 0.005), with no difference during Period 3 (Days 57-84). INVR results were generally more favorable with trimethobenzamide than placebo in Period 1 and significantly more favorable in Period 2. The majority of subjects in both groups achieved an "on" response after apomorphine injection at all assessments. No significant differences were found between groups for UPDRS motor scores. No added safety risk with concomitant use of trimethobenzamide and apomorphine was found.

Conclusion: Our data suggest that trimethobenzamide helps reduce nausea/vomiting during the first 8 weeks of apomorphine therapy, but is generally not needed thereafter. Trimethobenzamide did not worsen parkinsonism nor affect "on" response after apomorphine injection.

Keywords: Apomorphine; Clinical trial; Nausea; Treatment; Trimethobenzamide; Vomiting.

Publication types

  • Clinical Trial, Phase IV
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Antiemetics / therapeutic use*
  • Apomorphine / adverse effects*
  • Apomorphine / therapeutic use
  • Benzamides / therapeutic use*
  • Dopamine Agonists / adverse effects
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Injections, Subcutaneous / adverse effects
  • Male
  • Middle Aged
  • Nausea / chemically induced*
  • Nausea / drug therapy*
  • Parkinson Disease / drug therapy
  • Severity of Illness Index
  • Time Factors
  • Vomiting / chemically induced*
  • Vomiting / drug therapy*
  • Young Adult

Substances

  • Antiemetics
  • Benzamides
  • Dopamine Agonists
  • Apomorphine
  • trimethobenzamide