Opicapone for the treatment of Parkinson’s disease: an update

Figures & data

Figure 1. The main steps of levodopa metabolism and important therapeutic targets and drugs. (3-MT – 3-methoxy-tyramine; 3-OMD – 3-O-methyldopa; AADC – aromatic amino acid decarboxylase; BBB – blood-brain barrier; COMT – catechol-O-methyltransferase; DA – dopamine; DOPAC – 3,4-dihydroxy-phenylacetic acid; ENT – entacapone; HVA – homovanillic acid; LD – levodopa; MAO – monoamine oxidase; OPC – opicapone; SAH – S-adenosyl homocysteine; SAM – S-adenosyl methionine; SLCO1B1 – solute carrier organic anion transporter family, member 1B1; TCP – tolcapone).

Box 1. Drug summary box.

Drug name	Opicapone
Phase	IV
Indication	Parkinson’s Disease
Pharmacology description	Catechol-O-methyltransferase inhibitor (third generation)
Route of administration	Oral
Chemical structure
Pivotal trial(s)	[21], BIPARK 1 and 2 [15,38] (NCT01568073; NCT01227655)

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Table 1. Clinical trials with OPC (AUC – area under the curve; BIPARK – efficacy and safety of BIA 9–1067 in idiopathic Parkinson’s disease patients; BZ – benserazide; CD – carbidopa; Cmin – minimum blood plasma concentration; COMT – catechol-O-methyltransferase; ENT – entacapone; LD – levodopa; OPC – opicapone; PD – Parkinson’s disease; PLC – placebo). Adapted from [14] with permission of Taylor & Francis. Data also derived from [7] and [10].

Study (reference)	Phase	Number of included patients	Purpose of study	Dose	Comparator	Duration	Relevant results
Almeida et al. [18]	I	64 healthy (male) volunteers	Pharmacokinetics, -dynamics, safety and tolerability	Single oral doses of OPC (10, 25, 50, 100, 200, 400, 800, 1200 mg)	PLC	1 day	Half-life (terminal) of OPC: 0.8 h to 3.2 h (50–1200 mg); Maximal COMT inhibition: 36.1 – 100% (10 – ≥ 200 mg) – 72 h post-dose: 5.9–54.6% (10–800 mg); Levodopa maximal concentration: 1.5–3.5 h.
Almeida et al. [18]	I	12 healthy (male) volunteers	Relationship between food and pharmacokinetics	Single oral doses of OPC (50 mg)		9 days	Cmax was significantly lower after standard breakfast compared to fasting (238–635 ng/mL). Mean terminal time: 1.2 h (fasting) and 3.4 h (fed).
Rocha et al. [20]	I	34 healthy (male) volunteers	Pharmacokinetics, -dynamics	Repeated oral doses of OPC once daily (5, 10, 20, 30 mg)	PLC	8 days	Half-life (terminal) of OPC: 1–1.4 h; Maximal COMT inhibition: between 3.8–7.7 h – 144 h post-dose: 16.3–20.3% COMT activity decrease (5–30 mg).
Rocha et al. [19]	I	80 healthy (male, female) volunteers	Levodopa pharmacokinetics	Repeated oral doses of OPC once daily (25, 50, 75 mg)	PLC or ENT	12 days	OPC significantly increase the Cmin of levodopa and AUC0–24. Compared to ENT, OPC provides a superior response.
Rocha et al. [34]	II	10 PD Patients	Pharmacokinetics, -dynamics, safety and tolerability	Single oral doses of OPC (25, 50, 100 mg)	PLC (LD/CD-BZ)	3 days	Levodopa plasma concentration increased after OPC treatment (dose-dependent). Significant decrease of ‘time to best ON’, but increase of ‘ON duration’ (18–25%/25–50 mg OPC/).
Ferreira et al. [21]	II	35 PD Patients	Pharmacokinetics, -dynamics, safety, tolerability, efficacy	Repeated oral doses of OPC (5, 15, 30 mg)	PLC (LD/CD-BZ)	28 days	Levodopa plasma concentration increased after OPC treatment (dose-dependent). OPC 30 mg: −145 minutes decrease in OFF time. OPC 15, 30 mg: significant increase in ‘ON time without dyskinesia’.
Ferreira et al. – BIPARK-I [15]	III	600 PD Patients	Safety and efficacy	Repeated oral doses of OPC (5, 25, 50 mg)	PLC, ENT	14–15 weeks	50 mg OPC: OFF time reduction was significant in comparison to PLC (−116.8 vs. −56 minutes); increase ON time without dyskinesia (PLC). 50 mg OPC showed non-inferiority in OFF-time reduction compared to ENT.
Ferreira et al. [36]	Open label extension of BIPARK-I study	495 PD Patients	Safety and efficacy	Repeated oral doses of OPC (5, 25, 50 mg)	PLC, ENT	1 year	Switch from PLC or ENT revealed: decrease of OFF time (−65 min/PLC/, −39 min/ENT/) and increase ON time without dyskinesia (43 min/PLC/, 45/ENT/).
Lees et al. – BIPARK-II [38]	III	427 PD Patients	Safety and efficacy	Repeated oral doses of OPC (25, 50 mg)	PLC	14–15 weeks	50 mg OPC: OFF time reduction was significant in comparison to PLC (−54 minutes); not significant increase in ON time without dyskinesia (25, 50 mg OPC vs. PLC).
Ferreira et al. [36]	Open label extension of BIPARK-II study	376 PD Patients	Safety and efficacy	Repeated oral doses of OPC (25, 50 mg)	PLC	1 year	Compared to the DB phase, the OFF time reduction was long-lasting, and the ON time increased by an additional 24.9 minutes.
OPTIPARK (NCT02847442)	IV	518 PD Patients	Safety and efficacy	Repeated oral doses of OPC (50 mg)		3 to 6 months

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