Strong phase II data supports the development of Validive (clonidine MBT) for severe oral mucositis (SOM) in oropharyngeal cancer (OPC)

In October 2015, the global phase II clinical trial results of Validive (clonidine MBT) were announced, demonstrating initial evidence of clinical activity and safety compared to placebo. The trial enrolled 183 patients and was conducted in more than thirty centers in Europe and in the U.S. This global, multi-center, double-blind, randomized, placebo-controlled, three-arm study (NCT01385748) compared the efficacy and safety of Validive (50 microgram (µg) and 100 µg) to placebo in patients with surgically resected HNC receiving chemoradiation therapy. Validive (clonidine MBT) and placebo were applied to the gum once daily 1-3 days prior to chemoradiotherapy until the end of chemoradiotherapy treatment.

The safety profile of Validive (clonidine MBT) was very good, with a similar number of adverse events between the placebo and Validive (100 μg) cohorts. However, patients treated with Validive (clonidine MBT) experienced less nausea and dysphagia compared to placebo.

Placebo (N=62) Validive® 50 μg (N=56) Validive® 100 μg (N=65) Validive® pooled doses (N=121)
Patients experienced at least one TEAE 61 ( 98.4%) 48 ( 87.3%) 60 ( 93.8%) 108 ( 90.8%)
Patients experienced at least one TEAE related to the study treatment 18 ( 29.0%) 14 ( 25.5%) 18 ( 28.1%) 32 ( 26.9%)
Patients experienced at least one severe TEAE (≥ grade 3) related to study treatment 4 ( 6.5%) 8 ( 14.5%) 4 ( 6.3%) 12 ( 10.1%)
Patients permanently removed from the study due to a TEAE 1 ( 1.6%) 3 ( 5.5%) 3 ( 4.7%) 6 ( 5.0%)
TEAE = treatment emergent adverse event (i.e. AE occuring or worsening during the study treatment phase)

Compliance and acceptability of the treatment found the average overall patient compliance to be 95%, with a median of 98%. Overall compliance according to patient diaries was similar in all treatment groups and consistent with the compliance according to the investigator’s evaluation

The analysis of OPC patients in this study showed:

  • The incidence of SOM (primary endpoint) was reduced by 26.3% (40% relative to placebo) in OPC patients treated with Validive (100 μg) (p=0.09)
  • Secondary endpoints of severe drinking, eating, and speaking limitations due to mouth and throat soreness (MTS) score >2 were reduced in the Validive (100 μg) treated cohort (p<0.05)
  • Decreases in other indicators of clinical benefit including decreased duration of SOM (15 days versus placebo), weight loss, decreased opiate use and increased cumulative dose of radiation received strongly favored the Validive (100 μg) treated cohort
  • A dose response was observed with the Validive (100 μg) dose demonstrating superiority over the Validive (50 μg) dose

The effect of Validive (clonidine MBT) on SOM was much greater in OPC compared to non-OPC patients in this phase II trial. The results of this trial support the further development of Validive (clonidine MBT) for the treatment of SOM in patients with OPC.

Development Strategy

Adaptive trial that will evaluate Validive (clonidine MBT)

Development Strategy