The results of a Phase 2 clinical trial of Validive (clonidine MBT) for the amelioration of oral mucositis in head and neck cancer patients treated with chemoradiation were recently published in the International Journal of Radiation Oncology and Biological Physics.1 The trial enrolled 183 patients with head and neck cancer (HNC) and was conducted in more than thirty centers in Europe and the U.S. This global, multi-center, double-blind, randomized, placebo-controlled, three-arm study (NCT01385748) compared the efficacy and safety of two doses of Validive (50 microgram (µg) and 100 µg) to placebo in patients with HNC receiving chemoradiation therapy.2 Validive and placebo were applied under the patient's upper lip once daily beginning 1 to 3 days prior to chemoradiotherapy and continuing until the end of chemoradiotherapy treatment.  Validive was concluded to be effective at decreasing the incidence of severe oral mucositis (SOM) compared to placebo in patients with HNC in this study.

The safety profile of Validive was similar to that of placebo. However, patients treated with Validive 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 occurring or worsening during the study treatment phase)

The mean overall patient compliance was approximately 90% across all treatment groups. 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 the OPC patients in this study (n=64) showed:

  • In the intent-to-treat population, the incidence of SOM (primary endpoint) was reduced by 26.3% (40% relative to placebo) in OPC patients treated with Validive (100 μg). 65.2% of OPC patients on placebo experienced SOM compared to only 38.9% of OPC patients on Validive (100 µg).
  • Median duration was decreased from 17 days in the placebo cohort to 0 days in the Validive (100 µg) treated cohort.
  • Validive (100 µg) reduced the risk of onset of SOM by 52% compared to placebo.
  • Secondary endpoints of severe drinking, eating, and speaking limitations due to mouth and throat soreness (MTS) score were reduced in the Validive (100 μg) treated cohort.
  • Other indicators of clinical benefit including weight loss, opiate use, and 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 a trend toward superiority over the Validive (50 μg) dose and placebo.

The effect of Validive (clonidine MBT) on SOM was much greater in OPC compared to non-OPC patients in this Phase 2 trial. The results of this trial support the further development of Validive for the treatment of SOM in patients with OPC.

Development Strategy

Adaptive trial that will evaluate Validive

Development Strategy