Efficacy and Safety Study of CVT-301 In Parkinson's Disease Patients With OFF Episodes

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Investigating the Efficacy and Safety of CVT 301 (Levodopa Inhalation Powder) in Parkinson's Disease Patients With Motor Response Fluctuations (OFF Phenomena) (SPAN-PD™)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02240030

Acronym

SPAN-PD™

Enrollment

351

Registered

2014-09-15

Start date

2014-11-30

Completion date

2016-12-31

Last updated

2019-05-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Idiopathic Parkinson's Disease

Keywords

Parkinson's Disease, Motor fluctuations, levodopa, inhaled drugs, OFF episodes

Brief summary

This randomized, multicenter, placebo-controlled, double-blind study will evaluate the efficacy and safety of inhaled CVT 301 compared with placebo in PD patients experiencing motor response fluctuations (OFF phenomena) as an outpatient (i.e., at home) and in the clinic. Patients who successfully complete this study will be eligible to enroll into a 12 month treatment extension (CVT-301-004E) study.

Interventions

DRUGCVT-301 Low Dose

DRUGCVT-301 High Dose

OTHERPlacebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

30 Years to 85 Years

Healthy volunteers

Inclusion criteria

* Idiopathic Parkinson's Disease (PD) diagnosed between the ages of 30 and 85 years; * Hoehn and Yahr Stage 1-3 in an on state; * Require levodopa-containing medication regimen at least 3 times during the waking day; * Experience motor fluctuations with a minimum of 2 hours of average daily off time per waking day (excluding early morning off time) and demonstrate levodopa responsiveness; * Are on stable PD medication regimen; * Total daily LD dose \<1600 mg/day; * Able to perform a spirometry maneuver in the ON and OFF states; * Normal cognition confirmed by MMSE score ≥25

Exclusion criteria

* Pregnant or lactating females; * Previous surgery for PD or plan to have stereotactic surgery during the study period; * History of psychotic symptoms requiring treatment, or suicide ideation or attempt within last year; * Known contraindication to the use of levodopa; * Any significant condition, severe concurrent disease, abnormality or finding that would make patients unsuitable or may compromise patient safety; * Any contraindication to performing routine spirometry.

Design outcomes

Primary

Measure	Time frame	Description
Unified Parkinson's Disease Rating Scale (UPDRS) Part III	30 minutes post-dose at week 12	Primary Efficacy Analysis: Change from Predose in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score at 30 Minutes post-dose at Week 12 for CVT-301 High Dose versus Placebo (ITT Population). UPDRS Part III ranges from 0 minimum to 86 maximum, with lower scores indicating better movement. Units on a scale.

Secondary

Measure	Time frame	Description
Proportion of Patients Achieving Resolution of an OFF to an ON State Within 60 Minutes.	at week 12	Examiner-assessed observation - Subject Achieving Resolution of an OFF to and ON state within 60 Minutes at TV4 - Observed
UPDRS Part III Motor Score at 20 Minutes	at week 12	Change from Predose in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score at 20 Minutes post-dose at Week 12 for CVT-301 High Dose versus Placebo (ITT Population) and CVT 301 Low Dose versus Placebo. UPDRS Part III ranges from 0 minimum to 86 maximum, with lower scores indicating better movement. Units on a scale.
Proportion of Subjects Who Improved PGIC With CVT-301 vs. Placebo at Week 12	week 12	Patient Global impression of change at treatment visit 4 (week 12) by improvement category. Seven point Likert scale ranging from 1= much worse to 7= much better.
UPDRS Part III at 10 Min.	week 12	Change from Predose in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score at 10 Minutes post-dose at Week 12 for CVT-301 High Dose versus Placebo (ITT Population). UPDRS Part III ranges from 0 minimum to 86 maximum, with lower scores indicating better movement. Units on a scale.
PD Patient Diary	post week 12	Change in total daily OFF times for 3 consecutive days prior to week 12 visit compared to 3 consecutive days prior to baseline visit. Participants recorded On or Off state in 30 minute intervals during waking hours.

Countries

Canada, Czechia, Poland, Spain, United States

Participant flow

Participants by arm

Arm	Count
CVT-301 Low Dose Capsules of levodopa inhalational powder used up to 5 times/day for OFF episodes for 3 months duration CVT-301	113
CVT-301 High Dose Capsules of levodopa inhalational powder used up to 5 times/day for OFF episodes for 3 months duration CVT-301	114
Placebo Capsules of inhalation-grade lactose used up to 5 times/day for OFF episodes for 3 months duration. CVT-301	112
Total	339

Baseline characteristics

Characteristic	CVT-301 Low Dose	CVT-301 High Dose	Placebo	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	59 Participants	56 Participants	57 Participants	172 Participants
Age, Categorical Between 18 and 65 years	54 Participants	58 Participants	55 Participants	167 Participants
Age, Continuous	63.9 years STANDARD_DEVIATION 9.24	63.5 years STANDARD_DEVIATION 7.97	62.6 years STANDARD_DEVIATION 8.83	63.3 years STANDARD_DEVIATION 8.69
Region of Enrollment Canada	9 Participants	2 Participants	9 Participants	20 Participants
Region of Enrollment Poland	18 Participants	29 Participants	19 Participants	66 Participants
Region of Enrollment Spain	0 Participants	2 Participants	3 Participants	5 Participants
Region of Enrollment United States	86 Participants	81 Participants	81 Participants	248 Participants
Sex: Female, Male Female	33 Participants	31 Participants	26 Participants	90 Participants
Sex: Female, Male Male	80 Participants	83 Participants	86 Participants	249 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 113	0 / 114	0 / 112
other Total, other adverse events	37 / 113	44 / 114	10 / 112
serious Total, serious adverse events	6 / 113	2 / 114	3 / 112

Outcome results

Primary

Unified Parkinson's Disease Rating Scale (UPDRS) Part III

Primary Efficacy Analysis: Change from Predose in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score at 30 Minutes post-dose at Week 12 for CVT-301 High Dose versus Placebo (ITT Population). UPDRS Part III ranges from 0 minimum to 86 maximum, with lower scores indicating better movement. Units on a scale.

Time frame: 30 minutes post-dose at week 12