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

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ClinicalTrials.gov Identifier: NCT02242487
Recruitment Status : Completed
First Posted : September 17, 2014
Results First Posted : July 30, 2019
Last Update Posted : August 14, 2019
Sponsor:
Information provided by (Responsible Party):
Acorda Therapeutics

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Idiopathic Parkinson's Disease
Intervention Drug: CVT-301
Enrollment 325
Recruitment Details  
Pre-assignment Details Safety population - Altogether, 325 patients were randomized and 312 patients received at least 1 dose of study drug and were included in the Safety Population. Thirteen patients were randomized but did not receive study drug.
Arm/Group Title CVT-301 Low Dose CVT-301 High Dose
Hide Arm/Group Description

Two capsules of 30 mg each (60 mg total) of levodopa inhalational powder orally inhaled up to 5 times/day for OFF episodes for 12 months duration

CVT-301

Two capsules of 42 mg each (84 mg total) of levodopa inhalational powder orally inhaled up to 5 times/day for OFF episodes for 12 months duration

CVT-301

Period Title: Overall Study
Started 161 164
Completed 99 117
Not Completed 62 47
Reason Not Completed
Adverse Event             13             15
Lack of Efficacy             4             6
Protocol Violation             2             0
Lost to Follow-up             2             1
Other - Miscellaneous             4             6
Withdrawal by Subject             37             19
Arm/Group Title CVT-301 Low Dose CVT-301 High Dose Total
Hide Arm/Group Description

60 mg (two capsules of 30 mg) of levodopa inhalational powder used up to 5 times/day for OFF episodes for 12 months duration

CVT-301

84 mg (two capsules of 42 mg) of levodopa inhalational powder used up to 5 times/day for OFF episodes for 12 months duration

CVT-301

Total of all reporting groups
Overall Number of Baseline Participants 153 159 312
Hide Baseline Analysis Population Description
Baseline Characteristics of 312 is based on the Safety Population of 325 participants randomized less 13 who were randomized and Not Dosed.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 153 participants 159 participants 312 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
71
  46.4%
80
  50.3%
151
  48.4%
>=65 years
82
  53.6%
79
  49.7%
161
  51.6%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 153 participants 159 participants 312 participants
63.9  (8.76) 62.9  (8.34) 63.4  (8.55)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 153 participants 159 participants 312 participants
Female
43
  28.1%
40
  25.2%
83
  26.6%
Male
110
  71.9%
119
  74.8%
229
  73.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 153 participants 159 participants 312 participants
American Indian or Alaska Native
0
   0.0%
1
   0.6%
1
   0.3%
Asian
1
   0.7%
5
   3.1%
6
   1.9%
Native Hawaiian or Other Pacific Islander
1
   0.7%
0
   0.0%
1
   0.3%
Black or African American
3
   2.0%
3
   1.9%
6
   1.9%
White
147
  96.1%
150
  94.3%
297
  95.2%
More than one race
1
   0.7%
0
   0.0%
1
   0.3%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 153 participants 159 participants 312 participants
Canada 4 4 8
Czechia 5 3 8
Poland 39 45 84
Spain 5 6 11
United States 100 101 201
BMI  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 153 participants 159 participants 312 participants
27.65  (4.820) 27.59  (4.790) 27.62  (4.797)
1.Primary Outcome
Title Pulmonary Safety of CVT-301 Change From Baseline for FEV1.
Hide Description To characterize the effects of CVT-301 on pulmonary safety, as assessed by spirometry FEV1 (forced expiratory volume in 1 second) by treatment group and Treatment Visit (TV). This study was a 12-month, dose-level blinded, multi-center study of 2 inhaled dose levels of CVT-301 for the treatment of up to 5 OFF periods per day in PD (Parkinson's Disease) patients experiencing motor fluctuations (OFF periods). Baseline is defined as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004 study and as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004E study for the rest of the patients.
Time Frame Change from baseline at 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population - Altogether, 325 patients were randomized and 312 patients received at least 1 dose of study drug and were included in the Safety Population. Thirteen patients were randomized but did not receive study drug.
Arm/Group Title CVT-301 DL1 CVT-301 DL2
Hide Arm/Group Description:
60 mg (two capsules of 30 mg each) of Levodopa Inhalational Powder (LIP) up to 5 times a day.
84 mg (two capsules of 42 mg each) of Levodopa inhalation powder (LIP) up to 5 times a day.
Overall Number of Participants Analyzed 153 159
Mean (Standard Deviation)
Unit of Measure: Liters
Baseline Number Analyzed 153 participants 159 participants
2.957  (0.6995) 3.117  (0.7735)
TV3 (Week 12) Number Analyzed 141 participants 149 participants
-0.059  (0.2321) -0.078  (0.2108)
TV4 (Week 24) Number Analyzed 119 participants 136 participants
-0.057  (0.1999) -0.058  (0.2136)
TV5 (Week 36) Number Analyzed 112 participants 125 participants
-0.076  (0.2155) -0.052  (0.2096)
TV6 (Week 52) Number Analyzed 105 participants 115 participants
-0.086  (0.2238) -0.097  (0.2230)
2.Primary Outcome
Title Pulmonary Safety for CVT-301 Change From Baseline for FVC.
Hide Description To characterize the effects of CVT-301 on pulmonary safety, as assessed by spirometry FVC, (forced vital capacity) by treatment group and Treatment Visit (TV). This study was a 12-month, dose-level blinded, multi-center study of 2 inhaled dose levels of CVT-301 for the treatment of up to 5 OFF periods per day in PD patients experiencing motor fluctuations (OFF periods). Baseline is defined as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004 study and as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004E study for the rest of the patients.
Time Frame Change from baseline at 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population - Safety population - Altogether, 325 patients were randomized and 312 patients received at least 1 dose of study drug and were included in the Safety Population. Thirteen patients were randomized but did not receive study drug.
Arm/Group Title CVT-301 DL1 CVT-301 DL2
Hide Arm/Group Description:
60 mg (two capsules of 30 mg each) of Levodopa Inhalational Powder (LIP) up to 5 times a day.
84 mg (two capsules of 42 mg each) of Levodopa inhalation powder (LIP) up to 5 times a day.
Overall Number of Participants Analyzed 153 159
Mean (Standard Deviation)
Unit of Measure: Liter
Baseline Number Analyzed 153 participants 159 participants
3.840  (0.9047) 4.045  (0.9811)
TV3 (Week 12) Number Analyzed 141 participants 149 participants
-0.064  (0.2575) -0.086  (0.2667)
TV4 (Week 24) Number Analyzed 119 participants 136 participants
-0.053  (0.2710) -0.062  (0.2688)
TV5 (Week 36) Number Analyzed 112 participants 125 participants
-0.089  (0.3051) -0.050  (0.2659)
TV6 (Week 52) Number Analyzed 105 participants 115 participants
-0.106  (0.2866) -0.089  (0.2747)
3.Primary Outcome
Title Pulmonary Safety for CVT-301 Change From Baseline for (FEV1/FVC).
Hide Description To characterize the effects of CVT-301 on pulmonary safety, as assessed by spirometry FEV1/FVC (FEV1-forced expiratory volume in 1 second and (FVC) forced vital capacity ratio) by treatment group and Treatment Visit (TV). This study was a 12-month, dose-level blinded, multi-center study of 2 inhaled dose levels of CVT-301 for the treatment of up to 5 OFF periods per day in PD (Parkinson's Disease) patients experiencing motor fluctuations (OFF periods). Baseline is defined as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004 study and as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004E study for the rest of the patients.
Time Frame Change from baseline at 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population - Safety population - Altogether, 325 patients were randomized and 312 patients received at least 1 dose of study drug and were included in the Safety Population. Thirteen patients were randomized but did not receive study drug.
Arm/Group Title CVT-301 DL1 CVT-301 DL2
Hide Arm/Group Description:
60 mg (two capsules of 30 mg each) of Levodopa Inhalational Powder (LIP) up to 5 times a day.
84 mg (two capsules of 42 mg each) of Levodopa inhalation powder (LIP) up to 5 times a day.
Overall Number of Participants Analyzed 153 159
Mean (Standard Deviation)
Unit of Measure: Ratio %
Baseline Number Analyzed 153 participants 159 participants
77.2  (5.24) 77.2  (6.00)
TV3 (Week 12) Number Analyzed 141 participants 149 participants
-0.2  (3.35) -0.3  (2.89)
TV4 (Week 24) Number Analyzed 119 participants 136 participants
-0.3  (3.64) -0.3  (2.91)
TV5 (Week 36) Number Analyzed 112 participants 125 participants
-0.3  (2.75) -0.3  (3.02)
TV6 (Week 52) Number Analyzed 105 participants 115 participants
-0.2  (3.36) -0.7  (3.51)
4.Secondary Outcome
Title Count of Patients Achieving Resolution of an OFF to an ON State Within 60 Minutes.
Hide Description Count of patients achieving resolution of an OFF to an ON state within 60 minutes after study drug is administered in the clinic, and maintaining the ON state at 60 minutes after study drug administration (per the examiner's subjective assessment).
Time Frame At Treatment Visit - TV6 (Week 52)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT (Intent-to-Treat) Population
Arm/Group Title CVT-301 DL1 CVT-301 DL2
Hide Arm/Group Description:
60 mg (two capsules of 30 mg each) of Levodopa Inhalational Powder (LIP) up to 5 times a day.
84 mg (two capsules of 42 mg each) of Levodopa inhalation powder (LIP) up to 5 times a day.
Overall Number of Participants Analyzed 144 153
Measure Type: Count of Participants
Unit of Measure: Participants
78
  54.2%
92
  60.1%
5.Secondary Outcome
Title Change From Baseline in OFF Time.
Hide Description Patient reported total daily OFF time and was assessed by the patient and recorded in the patient Diary. An "OFF state" is defined as the time when medication is not providing benefit with respect to mobility, slowness, and stiffness. OFF episodes may be heralded by non-motor symptoms (e.g., pain, anxiety) prior to the appearance of motor symptoms. Patients will record their ON and OFF states in their diaries at home.
Time Frame Change from baseline through 12 months duration of outpatient use
Hide Outcome Measure Data
Hide Analysis Population Description
ITT - (Intent-to-Treat) Population. Patients who discontinue the study prior to a treatment visit are not included in the analysis for that treatment visit. Therefore, the number of patients decreases with each successive treatment visit.
Arm/Group Title CVT-301 DL1 CVT-301 DL2
Hide Arm/Group Description:
60 mg (two capsules of 30 mg each) of Levodopa Inhalation Powder (LIP)
84 mg (two capsules of 42 mg each) of Levodopa inhalation powder (LIP)
Overall Number of Participants Analyzed 144 153
Least Squares Mean (Standard Error)
Unit of Measure: Hours
TV2 (Week 4) Number Analyzed 137 participants 143 participants
-0.33  (0.221) -0.55  (0.217)
TV3 (Week 12) Number Analyzed 133 participants 139 participants
-0.23  (0.232) -0.38  (0.227)
TV4 (Week 24) Number Analyzed 114 participants 130 participants
-0.65  (0.235) -0.73  (0.227)
TV5 (Week 36) Number Analyzed 102 participants 116 participants
-0.49  (0.238) -0.92  (0.230)
TV6 (Week 52) Number Analyzed 94 participants 110 participants
-0.70  (0.239) -0.88  (0.229)
Time Frame 12-month period
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title CVT-301 Low Dose CVT-301 HIgh Dose
Hide Arm/Group Description 60 mg (two capsules of 30 mg each) of Levodopa Inhalational Powder (LIP) up to 5 times a day for OFF episodes for 12 months duration. 84 mg (two capsules of 42 mg each) of Levodopa inhalation powder (LIP) up to 5 times a day for OFF episodes for 12 months duration.
All-Cause Mortality
CVT-301 Low Dose CVT-301 HIgh Dose
Affected / at Risk (%) Affected / at Risk (%)
Total   0/153 (0.00%)      0/159 (0.00%)    
Hide Serious Adverse Events
CVT-301 Low Dose CVT-301 HIgh Dose
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   22/153 (14.38%)      13/159 (8.18%)    
Cardiac disorders     
Angina pectoris  1  2/153 (1.31%)  2 0/159 (0.00%)  0
Atrial fibrillation  1  1/153 (0.65%)  1 1/159 (0.63%)  1
Mycardial infarction  1  0/153 (0.00%)  0 1/159 (0.63%)  1
Sinus node dysfunction  1  1/153 (0.65%)  1 0/159 (0.00%)  0
Endocrine disorders     
Goitre  1  0/153 (0.00%)  0 1/159 (0.63%)  1
Gastrointestinal disorders     
Dysphagia  1  1/153 (0.65%)  1 0/159 (0.00%)  0
Gastrointestinal haemorrhage  1  1/153 (0.65%)  1 0/159 (0.00%)  0
Gastrooesophageal reflux disease  1  1/153 (0.65%)  1 0/159 (0.00%)  0
Inguinal hernia  1  0/153 (0.00%)  0 1/159 (0.63%)  1
Intestinal obstruction  1  0/153 (0.00%)  0 1/159 (0.63%)  1
Megacolon  1  0/153 (0.00%)  0 1/159 (0.63%)  1
Naseau  1  1/153 (0.65%)  1 0/159 (0.00%)  0
Oesophageal achalasia  1  1/153 (0.65%)  1 0/159 (0.00%)  0
Pancreatitis  1  0/153 (0.00%)  0 1/159 (0.63%)  1
Vomititng  1  1/153 (0.65%)  1 0/159 (0.00%)  0
General disorders     
Chest pain  1  0/153 (0.00%)  0 1/159 (0.63%)  1
Oedema peripheral  1  1/153 (0.65%)  1 0/159 (0.00%)  0
Infections and infestations     
Clostridium difficile infection  1  0/153 (0.00%)  0 1/159 (0.63%)  1
Hepatitis C  1  1/153 (0.65%)  1 0/159 (0.00%)  0
Necrotising soft tissue infection  1  1/153 (0.65%)  1 0/159 (0.00%)  0
Pneumonia  1  1/153 (0.65%)  1 0/159 (0.00%)  0
Urinary tract infection  1  1/153 (0.65%)  1 0/159 (0.00%)  0
Injury, poisoning and procedural complications     
Hip fracture  1  2/153 (1.31%)  2 0/159 (0.00%)  0
Radius fracture  1  1/153 (0.65%)  1 1/159 (0.63%)  1
Concussion  1  1/153 (0.65%)  1 0/159 (0.00%)  0
Fall  1  1/153 (0.65%)  1 0/159 (0.00%)  0
Femoral neck fracture  1  0/153 (0.00%)  0 1/159 (0.63%)  1
Rib fracture  1  1/153 (0.65%)  1 0/159 (0.00%)  0
Wound dehiscence  1  1/153 (0.65%)  1 0/159 (0.00%)  0
Metabolism and nutrition disorders     
Dehydration  1  1/153 (0.65%)  1 0/159 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Osteoarthritis  1  3/153 (1.96%)  3 0/159 (0.00%)  0
Intervertebral disc protrusion  1  1/153 (0.65%)  1 1/159 (0.63%)  1
Intervertebral disc degeneration  1  0/153 (0.00%)  0 1/159 (0.63%)  1
Osteoporotic fracture  1  0/153 (0.00%)  0 1/159 (0.63%)  1
Spinal column stenosis  1  0/153 (0.00%)  0 1/159 (0.63%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Prostrate cancer  1  1/153 (0.65%)  1 0/159 (0.00%)  0
Prostrate cancer metastatic  1  0/153 (0.00%)  0 1/159 (0.63%)  1
Nervous system disorders     
Central nervous system lesion  1  0/153 (0.00%)  0 1/159 (0.63%)  1
Metabolic encephalopathy  1  1/153 (0.65%)  1 0/159 (0.00%)  0
Parkinson's disease  1  1/153 (0.65%)  1 0/159 (0.00%)  0
Presyncope  1  1/153 (0.65%)  2 0/159 (0.00%)  0
Product Issues     
Device connection tissue  1  1/153 (0.65%)  1 0/159 (0.00%)  0
Psychiatric disorders     
Impulse-control disorder  1  0/153 (0.00%)  0 1/159 (0.63%)  1
Suicide threat  1  0/153 (0.00%)  0 1/159 (0.63%)  1
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  2/153 (1.31%)  2 0/159 (0.00%)  0
Acute respiratory failure  1  1/153 (0.65%)  1 0/159 (0.00%)  0
Surgical and medical procedures     
Bone graft  1  0/153 (0.00%)  0 1/159 (0.63%)  1
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
CVT-301 Low Dose CVT-301 HIgh Dose
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   81/153 (52.94%)      69/159 (43.40%)    
Infections and infestations     
Upper respiratory tract infection  1  10/153 (6.54%)  10 12/159 (7.55%)  13
Nasopharyngitis  1  8/153 (5.23%)  8 4/159 (2.52%)  5
Injury, poisoning and procedural complications     
Fall  1  24/153 (15.69%)  26 17/159 (10.69%)  22
Musculoskeletal and connective tissue disorders     
Back pain  1  8/153 (5.23%)  9 3/159 (1.89%)  4
Nervous system disorders     
Dyskinesia  1  6/153 (3.92%)  6 10/159 (6.29%)  11
Respiratory, thoracic and mediastinal disorders     
Cough  1  25/153 (16.34%)  28 23/159 (14.47%)  27
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding the study results for a period up to 30 days from the date the communication is submitted to the sponsor. The sponsor shall have the right to defer proposed publication an additional 60 days from the end of the review period. The sponsor cannot require changes to the communication and cannot unilaterally extend the embargo.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Charles Oh, Senior Vice President - Clinical Development
Organization: Acorda Therapeutics
Phone: 914-326-5455
EMail: coh@acorda.com
Layout table for additonal information
Responsible Party: Acorda Therapeutics
ClinicalTrials.gov Identifier: NCT02242487    
Other Study ID Numbers: CVT-301-004E
First Submitted: September 15, 2014
First Posted: September 17, 2014
Results First Submitted: June 12, 2019
Results First Posted: July 30, 2019
Last Update Posted: August 14, 2019