Istradefylline for OFF Episodes in Parkinson’s Disease: A US Perspective of Common Clinical Scenarios

Figures & data

Table 1 Treatment-Emergent Adverse Events (>5% and of Special Interest) in the Pooled Analysis of Four Clinical Trials of Istradefylline Versus Placebo

	Placebo (N=426)	Istradefylline 20 mg/day (N=356)	Istradefylline 40 mg/day (N=378)
Any TEAE	278 (65.3%)	241 (67.7%)	263 (69.6%)
Dyskinesia	32 (7.5%)	52 (14.6%)	63 (16.7%)
Orthostatic hypotension	23 (5.4%)	24 (6.7%)	26 (6.9%)
Falls	40 (9.4%)	23 (6.5%)	26 (6.9%)
Nausea and vomiting	20 (4.7%)	17 (4.8%)	26 (6.9%)
Nausea	20 (4.7%)	15 (4.2%)	24 (6.3%)
Hallucination	12 (2.8%)	8 (2.2%)	22 (5.8%)
Dizziness	16 (3.8%)	11 (3.1%)	21 (5.6%)
Constipation	12 (2.8%)	19 (5.3%)	21 (5.6%)
Insomnia	15 (3.5%)	2 (0.6%)	21 (5.6%)
Viral upper respiratory tract infection	20 (4.7%)	20 (4.7%)	20 (5.3%)
Somnolence*	13 (3.1%)	15 (4.2%)	8 (2.1%)
Increased liver enzymes*	11 (2.6%)	3 (0.8%)	7 (1.9%)
Sleep disturbance*	3 (0.7%)	3 (0.8%)	6 (1.6%)
Neutropenia*	0	1 (0.3%)	2 (0.5%)
Sleep attack*	0	1 (0.3%)	1 (0.3%)
Impulse control disorder*	0	0	1 (0.3%)

Note: *Adverse event of special interest.

Abbreviation: TEAE, treatment-emergent adverse event.

Figure 1 Reduction in OFF time and increases in good ON time (ON without troublesome dyskinesia) from the four randomized controlled studies (istradefylline versus placebo) that led to FDA approval. Study 1, 6002-US-005;²⁵ Study 2, 6002-US-013; Study 3, 6002-0608;³⁰ Study 4, 6002-009.³¹

Figure 2 Summary of efficacy outcomes from the four randomized controlled studies (istradefylline versus placebo) that led to FDA approval. Study 1, 6002-US-005;²⁵ Study 2, 6002-US-013;40 Study 3, 6002-0608;³⁰ Study 4, 6002-009.³¹

Table 2 Post-Marketing Clinical Research to Evaluate Parkinson’s Disease Symptoms in Japan

Target	N	Duration	Observation	Reference
Postural abnormality	21	3 months	Half (50%) of patients with postural abnormalities at baseline showed improvement after 3 months’ treatment with istradefylline	Suzuki et al 2018^Citation84
	4	2–8 months	Three of four patients with postural deformities and preserved paraspinal muscle volume showed significant improvement with istradefylline following dopamine agonist withdrawal	Fujioka et al 2019^Citation85
Gait disorder	14	1 month	Freezing of Gait Questionnaire (FOG-Q) scores were significantly lower after 1 month of istradefylline treatment versus baseline	Matsuura et al 2018^Citation64
	31	12 weeks	MDS-UPDRS Part III gait-related total scores significantly decreased at weeks 4–12 from baseline, with significant improvements in gait, freezing of gait, and postural stability. At week 12, there were significant improvements in FOG-Q, new FOG-Q, and overall movement per 48 h measured by portable gait rhythmogram	Iijima et al 2019^Citation86
Urinary disturbance	14 (male)	1 year	Significant improvements were observed on urinary questionnaires. Night-time urinary frequency and the percentage of the nocturnal urine volume also improved significantly at 3 months’ administration (p<0.01)	Kitta et al 2018^Citation87
Mood disorders	30	12 weeks	Following administration of istradefylline, the scores on the Snaith–Hamilton Pleasure Scale Japanese version (SHAPS-J), Apathy scale, and Beck Depression Inventory significantly improved over time	Nagayama et al 2019^Citation88

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