Pharmacokinetic drug evaluation of CVT-301 for the treatment of Parkinson’s disease

ABSTRACT

Introduction: Levodopa (LD), in combination with a decarboxylase inhibitor, is a mainstay and the most effective therapeutic agent in the treatment of Parkinson’s disease (PD). Unfortunately, during chronic treatment with this agent, ON–OFF phenomena and dyskinesia appear. Despite the many medical treatment options available, unpredictable OFF episodes can still occur and be severe and disabling. A rescue therapy that provides a rapid and predictable ON response for patients with OFF periods would be of great value for such patients.

Areas covered: CVT-301 is a self-administered dry powder aerosol inhaled formulation of LD that is being developed as a self-administered treatment for OFF periods. The PK profile of CVT-301, the efficacy, and the safety highlighted in randomized clinical trials will be reviewed.

Expert opinion: CVT-301 may offer several potential advantages including increased systemic bioavailability through pulmonary absorption, rapid onset of action, avoidance of first-pass drug metabolism and less plasma-level variability.

List of Abbreviations: PD: Parkinson’s disease; LD: Levodopa; CD: Carbidopa; AADC: aromatic L-amino acid decarboxylase; IR: immediate-release; FPD: fine particle dose; GI: gastrointestinal; PK: pharmacokinetic; CVs: coefficient of variation; UPDRS: Unified Parkinson’s Disease Rating Scale; AEs: adverse events; FEV: forced expiratory volume; FVC: forced vital capacity; DL_CO: diffuse lung CO ; t_max: time to maximum concentration

KEYWORDS:

• Levodopa
• Parkinson’s disease
• CVT-301
• motor fluctuations
• ON–OFF
• dyskinesia
• inhalable levodopa

Declaration of interest

F Stocchi has received funding from GSK, NOVARTIS, ORION, TEVA ITALIA, LUNDBECK, MERCK, SERONO, SOLVAY, EISAI, ZAMBON, CHIESI, SERVIER, UCB, BIAL, BIOGEN, and IMPAX. L Vacca has received funding from ZAMBON, CHIESI, and UCB. M Torti has received funding from ZAMBON, CHIESI, and UCB. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.