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Therapeutic Potential for Intranasal Levodopa in Parkinson's Disease -Off Reversal (THOR201)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03541356
Recruitment Status : Completed
First Posted : May 30, 2018
Results First Posted : August 12, 2020
Last Update Posted : August 12, 2020
Sponsor:
Information provided by (Responsible Party):
Impel NeuroPharma Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Sequential Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Parkinson's Disease
Interventions Combination Product: Placebo
Combination Product: L-dopa 35 mg
Combination Product: L-dopa 70mg
Combination Product: L-dopa 140 mg
Combination Product: L-dopa 70mg/carbidopa 7mg
Enrollment 32
Recruitment Details Parkinson's disease patients at movement disorder clinics in Australia
Pre-assignment Details Confirmation of L-dopa responsiveness at Visit 2, prior to randomization
Arm/Group Title Placebo L-dopa 35 mg L-dopa 70 mg L-dopa 140 mg L-dopa 70 mg/Carbidopa 7 mg
Hide Arm/Group Description Placebo: Delivered via the I231 POD (Precision Olfactory Delivery) device L-dopa 35 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril L-dopa 70mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril L-dopa 140 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril L-dopa 70mg/carbidopa 7mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
Period Title: Overall Study
Started 8 6 6 6 6
Completed 8 6 6 6 6
Not Completed 0 0 0 0 0
Arm/Group Title Placebo L-dopa 35 mg L-dopa 70 mg L-dopa 140 mg L-dopa 70 mg/Carbidopa 7 mg Total
Hide Arm/Group Description Placebo: Delivered via the I231 POD (Precision Olfactory Delivery) device L-dopa 35 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril L-dopa 70mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril L-dopa 140 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril L-dopa 70mg/carbidopa 7mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril Total of all reporting groups
Overall Number of Baseline Participants 8 6 6 6 6 32
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants 32 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
6
  75.0%
3
  50.0%
1
  16.7%
3
  50.0%
5
  83.3%
18
  56.3%
>=65 years
2
  25.0%
3
  50.0%
5
  83.3%
3
  50.0%
1
  16.7%
14
  43.8%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants 32 participants
Female
3
  37.5%
2
  33.3%
2
  33.3%
2
  33.3%
3
  50.0%
12
  37.5%
Male
5
  62.5%
4
  66.7%
4
  66.7%
4
  66.7%
3
  50.0%
20
  62.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants 32 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
8
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
32
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants 32 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
  25.0%
2
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
4
  12.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
6
  75.0%
4
  66.7%
6
 100.0%
6
 100.0%
6
 100.0%
28
  87.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Australia Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants 32 participants
8 6 6 6 6 32
1.Primary Outcome
Title Number of Participants With Treatment Emergent Adverse Events
Hide Description Assessment of treatment emergent adverse events after single dosing with INP103 (L-dopa or L-dopa/carbidopa)
Time Frame 7 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo L-dopa 35 mg L-dopa 70 mg L-dopa 140 mg L-dopa 70 mg/Carbidopa 7 mg
Hide Arm/Group Description:
Placebo: Delivered via the I231 POD (Precision Olfactory Delivery) device
L-dopa 35 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril
L-dopa 70mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
L-dopa 140 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril
L-dopa 70mg/carbidopa 7mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
Overall Number of Participants Analyzed 8 6 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
5
  62.5%
5
  83.3%
3
  50.0%
4
  66.7%
5
  83.3%
2.Secondary Outcome
Title AUC0-2hr for L-dopa
Hide Description Area under the Plasma Concentration-time Curve for L-dopa from Time = 0 to Time = 2 hours post dose. For the L-dopa 35 mg, L-dopa 70 mg, L-dopa 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For the L-dopa 70 mg/carbidopa 7 mg treatment arm, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose.
Time Frame For L-dopa 35 mg, 70 mg, 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 min
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects who received L-dopa or L-dopa/carbidopa. Placebo subjects therefore not included.
Arm/Group Title L-dopa 35 mg L-dopa 70 mg L-dopa 140 mg L-dopa 70 mg/Carbidopa 7 mg
Hide Arm/Group Description:
L-dopa 35 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril
L-dopa 70mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
L-dopa 140 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril
L-dopa 70mg/carbidopa 7mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
Overall Number of Participants Analyzed 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: hours*ng/mL
240.71  (117.819) 463.49  (260.093) 725.29  (456.566) 552.75  (177.979)
3.Secondary Outcome
Title Cmax of L-dopa
Hide Description Maximum Observed Plasma Concentration of L-dopa from Time = 0 to Time = 2 hours post dose. For the L-dopa 35 mg, L-dopa 70 mg, L-dopa 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For the L-dopa 70 mg/carbidopa 7 mg treatment arm, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose.
Time Frame For L-dopa 35 mg, 70 mg, 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects who received L-dopa. Placebo subjects not included.
Arm/Group Title L-dopa 35 mg L-dopa 70 mg L-dopa 140 mg L-dopa 70 mg/Carbidopa 7 mg
Hide Arm/Group Description:
L-dopa 35 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril
L-dopa 70mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
L-dopa 140 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril
L-dopa 70mg/carbidopa 7mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
Overall Number of Participants Analyzed 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: ng/mL
185.80  (78.144) 362.68  (195.265) 643.65  (462.469) 445.75  (183.746)
4.Secondary Outcome
Title Tmax of L-dopa
Hide Description Time to Reach the Maximum Plasma Concentration (Cmax) of L-dopa
Time Frame For L-dopa 35 mg, 70 mg, 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects who received L-dopa. Placebo subjects not included.
Arm/Group Title L-dopa 35 mg L-dopa 70 mg L-dopa 140 mg L-dopa 70 mg/Carbidopa 7 mg
Hide Arm/Group Description:
L-dopa 35 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril
L-dopa 70mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
L-dopa 140 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril
L-dopa 70mg/carbidopa 7mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
Overall Number of Participants Analyzed 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: minutes
60.17  (37.950) 66.00  (38.735) 70.00  (15.505) 92.00  (27.481)
5.Secondary Outcome
Title Mean Change From Baseline in MDS-UPDRS Score Over 2 Hours for C1, C2, C3 and Change From Baseline at 30, 60, 90, 120 Minutes for C4, in MDS-UPDRS Part III Score
Hide Description MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Maximum score is 132, minimum is zero. High score means worse outcome. For the L-dopa 35 mg, L-dopa 70 mg, L-dopa 140 mg treatment groups, assessment occurred at pre-dose, 15, 30, 45, 60, 90 and 120 minutes post-dose. For the L-dopa 70 mg/carbidopa 7 mg treatment arm, assessment occurred at pre-dose, 30, 60, 90 and 120 minutes post-dose.
Time Frame For L-dopa 35 mg, 70 mg, 140 mg, assessment occurred at pre-dose, 15, 30, 45, 60, 90 and 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, assessment occurred at pre-dose, 30, 60, 90 and 120 minutes post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were analyzed.
Arm/Group Title Placebo L-dopa 35 mg L-dopa 70 mg L-dopa 140 mg L-dopa 70 mg/Carbidopa 7 mg
Hide Arm/Group Description:
Placebo: Delivered via the I231 POD (Precision Olfactory Delivery) device
L-dopa 35 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril
L-dopa 70mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
L-dopa 140 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril
L-dopa 70mg/carbidopa 7mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
Overall Number of Participants Analyzed 8 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: score on a scale
15 minutes Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants
-3.5  (3.89) -4.5  (4.46) 0.8  (9.20) -9.0  (6.16) NA [1]   (NA)
30 minutes Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants
-8.5  (6.52) -6.7  (4.89) -8.5  (9.09) -12.7  (7.79) -3.7  (3.83)
45 minutes Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants
-13.5  (7.09) -4.7  (4.03) -12.8  (11.05) -13.7  (8.91) NA [1]   (NA)
60 minutes Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants
-12.5  (7.87) -6.8  (4.54) -15.7  (9.58) -13.5  (8.29) -0.8  (10.63)
90 minutes Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants
-10.8  (9.35) -10.3  (13.56) -15.5  (10.03) -9.0  (5.76) -3.7  (10.76)
120 minutes Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants
-8.8  (10.61) -11.0  (9.47) -13.8  (11.97) -7.2  (9.09) -3.2  (9.22)
[1]
Participants in this arm were not tested at this time point.
6.Secondary Outcome
Title Time to Response (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline)
Hide Description MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe.
Time Frame 2 hours
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were analyzed.
Arm/Group Title Placebo L-dopa 35 mg L-dopa 70 mg L-dopa 140 mg L-dopa 70 mg/Carbidopa 7 mg
Hide Arm/Group Description:
Placebo: Delivered via the I231 POD (Precision Olfactory Delivery) device
L-dopa 35 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril
L-dopa 70mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
L-dopa 140 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril
L-dopa 70mg/carbidopa 7mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
Overall Number of Participants Analyzed 8 6 6 6 6
Median (95% Confidence Interval)
Unit of Measure: minutes
45.0 [1] 
(35.0 to NA)
NA [2] 
(40.0 to NA)
54.0 [1] 
(15.0 to NA)
30.0 [1] 
(15.0 to NA)
NA [2] 
(32.0 to NA)
[1]
The upper bound of the 95% CI could not be calculated due to the number of participants not achieving a response in the analysis time frame
[2]
The median and the upper bound of the 95% CI could not be calculated due to the number of participants not achieving a response in the analysis time frame
7.Secondary Outcome
Title Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline)
Hide Description MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe.
Time Frame From time = 0 to 2 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were analyzed.
Arm/Group Title Placebo L-dopa 35 mg L-dopa 70 mg L-dopa 140 mg L-dopa 70 mg/Carbidopa 7 mg
Hide Arm/Group Description:
Placebo: Delivered via the I231 POD (Precision Olfactory Delivery) device
L-dopa 35 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril
L-dopa 70mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
L-dopa 140 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril
L-dopa 70mg/carbidopa 7mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
Overall Number of Participants Analyzed 8 6 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
15 minutes Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants
0
   0.0%
0
   0.0%
1
  16.7%
2
  33.3%
NA [1] 
30 minutes Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants
3
  37.5%
1
  16.7%
1
  16.7%
5
  83.3%
1
  16.7%
45 minutes Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants
4
  66.7%
1
  16.7%
3
  50.0%
5
  83.3%
NA [1] 
60 minutes Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants
6
  75.0%
1
  16.7%
4
  66.7%
5
  83.3%
2
  33.3%
90 minutes Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants
6
  75.0%
2
  33.3%
5
  83.3%
5
  83.3%
3
  50.0%
120 minutes Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants
6
  75.0%
2
  33.3%
5
  83.3%
5
  83.3%
3
  50.0%
[1]
Subjects in this arm were not analyzed at this time point.
8.Secondary Outcome
Title Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores
Hide Description MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe.
Time Frame For L-dopa 35 mg, 70 mg, 140 mg, assessments were made at pre-dose, 15, 30, 45, 60, 90, 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, assessments were made at pre-dose, 50, 60, 90, 120 minutes post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were included in the analysis
Arm/Group Title Placebo L-dopa 35 mg L-dopa 70 mg L-dopa 140 mg L-dopa 70 mg/Carbidopa 7 mg
Hide Arm/Group Description:
Placebo: Delivered via the I231 POD (Precision Olfactory Delivery) device
L-dopa 35 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril
L-dopa 70mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
L-dopa 140 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril
L-dopa 70mg/carbidopa 7mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
Overall Number of Participants Analyzed 8 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: change in score*minutes
15 minutes Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants
-26.25  (29.144) -33.50  (33.697) 7.00  (69.206) -67.50  (46.233) NA [1]   (NA)
30 minutes Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants
-237.63  (276.197) -138.58  (138.105) -50.50  (203.053) -232.83  (153.638) -230.08  (250.832)
45 minutes Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants
-264.92  (178.969) -201.92  (162.256) -210.50  (334.216) -426.83  (274.566) NA [1]   (NA)
60 minutes Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants
-573.88  (371.782) -296.50  (241.271) -424.25  (464.545) -630.58  (401.947) -295.25  (412.042)
90 minutes Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants
-919.75  (530.872) -575.17  (486.241) -896.67  (671.116) -968.08  (587.629) -362.75  (676.456)
120 minutes Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants
-1215.75  (765.287) -903.67  (804.196) -1324.83  (863.122) -1210.58  (714.512) -465.25  (932.842)
[1]
Participants in this arm were not assessed at this time point.
9.Secondary Outcome
Title Mean Maximum Change From Baseline in MDS-UPDRS Part III Score
Hide Description MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The total of the subscales has a maximum value of 132 and a minimum value of zero. Lower scores indicate better motor function. A negative change from baseline indicates improved motor function.
Time Frame From time = 0 to 2 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects were included in this analysis
Arm/Group Title Placebo L-dopa 35 mg L-dopa 70 mg L-dopa 140 mg L-dopa 70 mg/Carbidopa 7 mg
Hide Arm/Group Description:
Placebo: Delivered via the I231 POD (Precision Olfactory Delivery) device
L-dopa 35 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril
L-dopa 70mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
L-dopa 140 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril
L-dopa 70mg/carbidopa 7mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
Overall Number of Participants Analyzed 8 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: score on a scale
-15.5  (6.35) -14.0  (11.15) -20.3  (11.18) -15.3  (8.12) -7.5  (6.72)
10.Secondary Outcome
Title Subjective Time to "ON" as Evaluated by the Investigator
Hide Description Investigators will evaluate subjects' fluctuations in motor functions at 15, 30, 45, 60, 90, 120, and 240 minutes post-dose to determine if they are "ON".
Time Frame 4 hours
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were included in the analysis
Arm/Group Title Placebo L-dopa 35 mg L-dopa 70 mg L-dopa 140 mg L-dopa 70 mg/Carbidopa 7 mg
Hide Arm/Group Description:
Placebo: Delivered via the I231 POD (Precision Olfactory Delivery) device
L-dopa 35 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril
L-dopa 70mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
L-dopa 140 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril
L-dopa 70mg/carbidopa 7mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
Overall Number of Participants Analyzed 8 6 6 6 6
Median (Full Range)
Unit of Measure: minutes
45.0
(30 to 240)
240.0 [1] 
(90 to NA)
30.0
(15 to 240)
30.0
(15 to 240)
240.0
(30 to 240)
[1]
One or more subjects in this arm did not achieve ON by the end of the assessment period. Therefore upper range was >240 minutes.
11.Secondary Outcome
Title Assessment of Time to "ON" as Evaluated by Subject Self-assessment
Hide Description Subjects were asked to provide self-assessments at 15, 30, 45, 60, 90, 120, and 240 minutes post-dose as to whether they considered themselves to be "ON".
Time Frame 4 hours
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were included in the analysis.
Arm/Group Title Placebo L-dopa 35 mg L-dopa 70 mg L-dopa 140 mg L-dopa 70 mg/Carbidopa 7 mg
Hide Arm/Group Description:
Placebo: Delivered via the I231 POD (Precision Olfactory Delivery) device
L-dopa 35 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril
L-dopa 70mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
L-dopa 140 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril
L-dopa 70mg/carbidopa 7mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
Overall Number of Participants Analyzed 8 6 6 6 6
Median (Full Range)
Unit of Measure: minutes
40.0
(15 to 240)
240.0 [1] 
(95 to NA)
39.0
(15 to 240)
30.0
(15 to 240)
232.5
(31 to 240)
[1]
One or more participants in this arm did not perceive themselves to be "ON" by the end of the assessment period, therefore the full range is 95 to >240 minutes
12.Secondary Outcome
Title AUC0-2h for Carbidopa
Hide Description Area under the concentration time curve for carbidopa
Time Frame Plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose and AUC calculated from these from time 0 to 120 minutes.
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects who received the combination of L-dopa/carbidopa
Arm/Group Title L-dopa 70 mg/Carbidopa 7 mg
Hide Arm/Group Description:
L-dopa 70mg/carbidopa 7mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: hours*ng/mL
114.80  (30.384)
13.Secondary Outcome
Title Cmax of Carbidopa
Hide Description Maximum concentration of carbidopa
Time Frame For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects who received L-dopa/carbidopa
Arm/Group Title L-dopa 70 mg/Carbidopa 7 mg
Hide Arm/Group Description:
L-dopa 70mg/carbidopa 7mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: ng/mL
80.23  (22.945)
14.Secondary Outcome
Title Tmax of Carbidopa
Hide Description Time to reach the maximum concentration of carbidopa
Time Frame For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects who received L-dopa/carbidopa
Arm/Group Title L-dopa 70 mg/Carbidopa 7 mg
Hide Arm/Group Description:
L-dopa 70mg/carbidopa 7mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: minutes
44.50  (13.882)
15.Secondary Outcome
Title Duration of Response, Where Response is Defined as an Improvement of 30% in MDS-UPDRS Part III Score From Baseline.
Hide Description MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Maximum score is 132, minimum is zero. High score means worse outcome.
Time Frame 2 hours
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were analyzed.
Arm/Group Title Placebo L-dopa 35 mg L-dopa 70 mg L-dopa 140 mg L-dopa 70 mg/Carbidopa 7 mg
Hide Arm/Group Description:
Placebo: Delivered via the I231 POD (Precision Olfactory Delivery) device
L-dopa 35 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril
L-dopa 70mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
L-dopa 140 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril
L-dopa 70mg/carbidopa 7mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
Overall Number of Participants Analyzed 8 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: minutes
66.9  (48.35) 23.3  (36.70) 57.3  (42.72) 37.5  (42.25) 15.0  (25.10)
Time Frame 7 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo L-dopa 35 mg L-dopa 70 mg L-dopa 140 mg L-dopa 70 mg/Carbidopa 7 mg
Hide Arm/Group Description Placebo: Delivered via the I231 POD (Precision Olfactory Delivery) device L-dopa 35 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril L-dopa 70mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril L-dopa 140 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril L-dopa 70mg/carbidopa 7mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
All-Cause Mortality
Placebo L-dopa 35 mg L-dopa 70 mg L-dopa 140 mg L-dopa 70 mg/Carbidopa 7 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/8 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)    
Hide Serious Adverse Events
Placebo L-dopa 35 mg L-dopa 70 mg L-dopa 140 mg L-dopa 70 mg/Carbidopa 7 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/8 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0.1%
Placebo L-dopa 35 mg L-dopa 70 mg L-dopa 140 mg L-dopa 70 mg/Carbidopa 7 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/8 (62.50%)      5/6 (83.33%)      3/6 (50.00%)      4/6 (66.67%)      5/6 (83.33%)    
Cardiac disorders           
tachycardia  1  1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Eye disorders           
lacrimation increased  1  0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
General disorders           
fatigue  1  1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
feeling abnormal  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
hyperthermia  1  0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Infections and infestations           
rhinitis  1  0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
urinary tract infection  1  0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Injury, poisoning and procedural complications           
procedural pain  1  0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Musculoskeletal and connective tissue disorders           
joint noise  1  0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
muscle spasms  1  1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Nervous system disorders           
headache  1  0/8 (0.00%)  0 2/6 (33.33%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
somnolence  1  0/8 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
dizziness  1  0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Respiratory, thoracic and mediastinal disorders           
upper respiratory tract infection  1  0/8 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0
rhinorrhoea  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0
sinus pain  1  0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1
cough  1  0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
dry throat  1  1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
dyspnoea  1  0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
nasal congestion  1  0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
nasal discomfort  1  1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
nasal dryness  1  0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
nasal oedema  1  0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
paranasal sinus discomfort  1  0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
paranasal sinus hyposecretion  1  0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
sneezing  1  1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Vascular disorders           
hypertension  1  1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
orthostatic hypotension  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
1
Term from vocabulary, MedDRA (19.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Karen Craig, PhD (Medical Writer)
Organization: Impel NeuroPharma
Phone: 206-568-1466
EMail: kcraig@impelnp.com
Layout table for additonal information
Responsible Party: Impel NeuroPharma Inc.
ClinicalTrials.gov Identifier: NCT03541356    
Other Study ID Numbers: INP103-201
First Submitted: April 5, 2018
First Posted: May 30, 2018
Results First Submitted: May 26, 2020
Results First Posted: August 12, 2020
Last Update Posted: August 12, 2020