Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 6 of 10 for:    SB-742457

Study Evaluating Intepirdine (RVT-101) in Subjects With Dementia With Lewy Bodies: The HEADWAY-DLB Study

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: NCT02669433
Recruitment Status : Completed
First Posted : February 1, 2016
Results First Posted : April 26, 2019
Last Update Posted : April 26, 2019
Sponsor:
Information provided by (Responsible Party):
Axovant Sciences Ltd.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Dementia With Lewy Bodies
Interventions Drug: RVT-101 35 mg
Drug: RVT-101 70 mg
Drug: Placebo
Enrollment 484
Recruitment Details  
Pre-assignment Details 484 participants signed consent and were screened for participation. Of these, 306 entered a 2-week single-blind placebo run-in period with treatment with placebo qd. There was an overlap between the participants from the run-in period and the participants that were randomized during the treatment period.
Arm/Group Title Placebo RVT-101 35 mg RVT-101 70 mg
Hide Arm/Group Description

Subjects dosed with two Placebo tablets

Placebo: once daily, oral, matching tablets

Subjects dosed with one Placebo tablet + 1 35 mg tablet of RVT-101

RVT-101 35 mg: once daily, oral, 35-mg tablets

Subjects dosed with two RVT-101 35 mg tablets

RVT-101 70 mg: once daily, oral, 35-mg tablets

Period Title: Overall Study
Started 91 89 89
Safety Population [1] 91 89 88
Intent to Treat (ITT) Population [2] 89 89 87
Per-Protocol Population [3] 78 79 82
Completers Population [4] 73 72 69
UPDRS Primary Population 87 87 84
Completed [5] 76 75 74
Not Completed 15 14 15
Reason Not Completed
Protocol Violation             0             4             1
Disease Progression             1             0             0
Physician Decision             1             1             0
Adverse Event             6             7             10
Sponsor Termination             1             0             1
Withdrawal by Subject             5             1             0
Withdrawal by Caregiver             1             0             2
Death             0             1             1
[1]
The Safety population included subjects who took at least 1 dose of double-blind study drug
[2]
Subjects took at least 1 dose of double-blind study drug and had at least 1 post-baseline assessment
[3]
Subjects in the ITT population who had no major protocol violations
[4]
Subjects in the ITT population who completed the study
[5]
Subjects who completed every visit per protocol
Arm/Group Title Placebo RVT-101 35 mg RVT-101 70 mg Total
Hide Arm/Group Description

Subjects dosed with two Placebo tablets

Placebo: once daily, oral, matching tablets

Subjects dosed with one Placebo tablet + 1 35 mg tablet of RVT-101

RVT-101 35 mg: once daily, oral, 35-mg tablets

Subjects dosed with two RVT-101 35 mg tablets

RVT-101 70 mg: once daily, oral, 35-mg tablets

Total of all reporting groups
Overall Number of Baseline Participants 91 89 88 268
Hide Baseline Analysis Population Description
Safety Population
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 91 participants 89 participants 88 participants 268 participants
73.6
(59 to 86)
73.0
(55 to 85)
73.0
(55 to 86)
73.0
(55 to 86)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
< 74 years Number Analyzed 91 participants 89 participants 88 participants 268 participants
45
  49.5%
45
  50.6%
45
  51.1%
135
  50.4%
>/= 74 years Number Analyzed 91 participants 89 participants 88 participants 268 participants
46
  50.5%
44
  49.4%
43
  48.9%
133
  49.6%
< 65 years Number Analyzed 91 participants 89 participants 88 participants 268 participants
7
   7.7%
9
  10.1%
12
  13.6%
28
  10.4%
>/=65 years Number Analyzed 91 participants 89 participants 88 participants 268 participants
84
  92.3%
80
  89.9%
76
  86.4%
240
  89.6%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 91 participants 89 participants 88 participants 268 participants
Female
20
  22.0%
22
  24.7%
15
  17.0%
57
  21.3%
Male
71
  78.0%
67
  75.3%
73
  83.0%
211
  78.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 91 participants 89 participants 88 participants 268 participants
Hispanic or Latino
4
   4.4%
6
   6.7%
0
   0.0%
10
   3.7%
Not Hispanic or Latino
86
  94.5%
83
  93.3%
86
  97.7%
255
  95.1%
Unknown or Not Reported
1
   1.1%
0
   0.0%
2
   2.3%
3
   1.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 91 participants 89 participants 88 participants 268 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
3
   3.4%
1
   1.1%
4
   1.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
4
   4.5%
0
   0.0%
4
   1.5%
White
90
  98.9%
81
  91.0%
85
  96.6%
256
  95.5%
More than one race
0
   0.0%
1
   1.1%
0
   0.0%
1
   0.4%
Unknown or Not Reported
1
   1.1%
0
   0.0%
2
   2.3%
3
   1.1%
BMI   [1] 
Mean (Full Range)
Unit of measure:  Kg/m^2
Number Analyzed 90 participants 89 participants 87 participants 266 participants
26.59
(15.8 to 39.2)
26.51
(16.8 to 42.1)
26.81
(18.6 to 41.6)
26.64
(15.8 to 42.1)
[1]
Measure Analysis Population Description: Data was missing for two subjects
1.Primary Outcome
Title Unified Parkinson’s Disease Rating Scale-Part III (UPDRS-III) Change From Baseline at Week 24
Time Frame Change from Baseline at 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
UPDRS Primary Population
Arm/Group Title Placebo RVT-101 35 mg RVT-101 70 mg
Hide Arm/Group Description:

Subjects dosed with two Placebo tablets

Placebo: once daily, oral, matching tablets

Subjects dosed with one Placebo tablet + 1 35 mg tablet of RVT-101

RVT-101 35 mg: once daily, oral, 35-mg tablets

Subjects dosed with two RVT-101 35 mg tablets

RVT-101 70 mg: once daily, oral, 35-mg tablets

Overall Number of Participants Analyzed 72 72 69
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.55  (1.039) 1.45  (1.025) -1.29  (1.056)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RVT-101 35 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.158
Comments The threshold for statistical significance was p=0.05
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.01
Confidence Interval (2-Sided) 95%
-4.80 to 0.79
Estimation Comments Placebo - active
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RVT-101 70 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6069
Comments The threshold for statistical significance was p=0.05
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
-2.08 to 3.55
Estimation Comments Placebo - active
2.Secondary Outcome
Title Alzheimer's Disease Assessment Scale - Cognitive Subscale 11 Items (ADAS-Cog-11) Change From Baseline at Week 24
Hide Description The 11-item ADAS-Cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place, and spontaneous speech. The ADAS-Cog-11 total score range is from 0 to 70, with a higher score indicating more severe cognitive impairment.
Time Frame Change from Baseline at 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo RVT-101 35 mg RVT-101 70 mg
Hide Arm/Group Description:

Subjects dosed with two Placebo tablets

Placebo: once daily, oral, matching tablets

Subjects dosed with one Placebo tablet + 1 35 mg tablet of RVT-101

RVT-101 35 mg: once daily, oral, 35-mg tablets

Subjects dosed with two RVT-101 35 mg tablets

RVT-101 70 mg: once daily, oral, 35-mg tablets

Overall Number of Participants Analyzed 73 73 71
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
1.68  (0.774) 2.15  (0.769) 1.01  (0.796)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RVT-101 35 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6531
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.47
Confidence Interval (2-Sided) 95%
-2.55 to 1.60
Estimation Comments Placebo - active
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RVT-101 70 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5274
Comments The threshold for statistical significance was p=0.05
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
-1.41 to 2.75
Estimation Comments Placebo - active
3.Secondary Outcome
Title Clinician’s Interview-Based Impression of Change Plus Caregiver Input (CIBIC+) Change From Baseline at Week 24
Hide Description To assess the effects of RVT-101 versus placebo on global function as measured by the Clinician’s Interview-Based Impression of Change Plus Caregiver Input (CIBIC+) after 24 weeks of treatment. CIBIC+ is recorded on a 7-point scale with a score of 4 indicating no change, scores above 4 indicating worsening, and scores below 4 indicating improvement.
Time Frame Change from Baseline at 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo RVT-101 35 mg RVT-101 70 mg
Hide Arm/Group Description:

Subjects dosed with two Placebo tablets

Placebo: once daily, oral, matching tablets

Subjects dosed with one Placebo tablet + 1 35 mg tablet of RVT-101

RVT-101 35 mg: once daily, oral, 35-mg tablets

Subjects dosed with two RVT-101 35 mg tablets

RVT-101 70 mg: once daily, oral, 35-mg tablets

Overall Number of Participants Analyzed 75 74 72
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
4.42  (0.127) 4.27  (0.128) 4.35  (0.131)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RVT-101 35 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3953
Comments The threshold for statistical significance was p=0.05
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.15
Confidence Interval (2-Sided) 95%
-0.2 to 0.5
Estimation Comments Placebo - active
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RVT-101 70 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7008
Comments The threshold for statistical significance was p=0.05
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
-0.28 to 0.42
Estimation Comments Placebo - active
Time Frame Screening through post treatment (up to 33 weeks)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo RVT-101 35 mg RVT-101 70 mg
Hide Arm/Group Description

Placebo

Placebo: once daily, oral, matching tablets

RVT-101 35 mg once daily

RVT-101 35 mg: once daily, oral, 35-mg tablets

RVT-101 70 mg once daily

RVT-101 70 mg: once daily, oral, 35-mg tablets

All-Cause Mortality
Placebo RVT-101 35 mg RVT-101 70 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/91 (1.10%)   1/89 (1.12%)   2/88 (2.27%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo RVT-101 35 mg RVT-101 70 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   11/91 (12.09%)   11/89 (12.36%)   13/88 (14.77%) 
Cardiac disorders       
Atrial Flutter  1  0/91 (0.00%)  1/89 (1.12%)  0/88 (0.00%) 
Trifascicular block  1  0/91 (0.00%)  0/89 (0.00%)  1/88 (1.14%) 
Gastrointestinal disorders       
Rectal Haemorrhage  1  0/91 (0.00%)  1/89 (1.12%)  1/88 (1.14%) 
Diverticulum intestinal haemorrhagic  1  0/91 (0.00%)  0/89 (0.00%)  1/88 (1.14%) 
Enteritis  1  1/91 (1.10%)  0/89 (0.00%)  0/88 (0.00%) 
Intestinal obstruction  1  0/91 (0.00%)  0/89 (0.00%)  1/88 (1.14%) 
Volvulus  1  0/91 (0.00%)  1/89 (1.12%)  0/88 (0.00%) 
Hepatobiliary disorders       
Cholecystitiis acute  1  1/91 (1.10%)  0/89 (0.00%)  0/88 (0.00%) 
Infections and infestations       
Urinary tract infection  1  2/91 (2.20%)  0/89 (0.00%)  1/88 (1.14%) 
Pneumonia  1  0/91 (0.00%)  0/89 (0.00%)  2/88 (2.27%) 
Sepsis  1  1/91 (1.10%)  1/89 (1.12%)  0/88 (0.00%) 
Escherichia urinary tract infection  1  0/91 (0.00%)  1/89 (1.12%)  0/88 (0.00%) 
Lower respiratory tract infection  1  1/91 (1.10%)  0/89 (0.00%)  0/88 (0.00%) 
Pyelonephritis  1  0/91 (0.00%)  0/89 (0.00%)  1/88 (1.14%) 
Urosepsis  1  0/91 (0.00%)  1/89 (1.12%)  0/88 (0.00%) 
Injury, poisoning and procedural complications       
Concussion  1  1/91 (1.10%)  0/89 (0.00%)  0/88 (0.00%) 
Facial bones fracture  1  0/91 (0.00%)  0/89 (0.00%)  1/88 (1.14%) 
Femur fracture  1  0/91 (0.00%)  1/89 (1.12%)  0/88 (0.00%) 
Spinal compression fracture  1  1/91 (1.10%)  0/89 (0.00%)  0/88 (0.00%) 
Subdural haematoma  1  0/91 (0.00%)  0/89 (0.00%)  1/88 (1.14%) 
Hip fracture  1  0/91 (0.00%)  1/89 (1.12%)  0/88 (0.00%) 
Metabolism and nutrition disorders       
Dehydration  1  1/91 (1.10%)  0/89 (0.00%)  0/88 (0.00%) 
Hyponatraemia  1  1/91 (1.10%)  0/89 (0.00%)  0/88 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Squamous cell carcinoma  1  2/91 (2.20%)  0/89 (0.00%)  0/88 (0.00%) 
Basal cell carcinoma  1  1/91 (1.10%)  0/89 (0.00%)  0/88 (0.00%) 
Prostatic adenoma  1  1/91 (1.10%)  0/89 (0.00%)  0/88 (0.00%) 
Nervous system disorders       
Ischaemic stroke  1  0/91 (0.00%)  1/89 (1.12%)  1/88 (1.14%) 
Dementia  1  1/91 (1.10%)  0/89 (0.00%)  0/88 (0.00%) 
Encephalopathy  1  0/91 (0.00%)  1/89 (1.12%)  0/88 (0.00%) 
Haemorrhagic stroke  1  0/91 (0.00%)  1/89 (1.12%)  0/88 (0.00%) 
Metabolic encephalopathy  1  0/91 (0.00%)  1/89 (1.12%)  0/88 (0.00%) 
Transient ischaemic attack  1  0/91 (0.00%)  1/89 (1.12%)  0/88 (0.00%) 
Psychiatric disorders       
Delirium  1  2/91 (2.20%)  0/89 (0.00%)  0/88 (0.00%) 
Depression  1  0/91 (0.00%)  1/89 (1.12%)  0/88 (0.00%) 
Hallucination, visual  1  0/91 (0.00%)  0/89 (0.00%)  1/88 (1.14%) 
Mental status change  1  1/91 (1.10%)  0/89 (0.00%)  0/88 (0.00%) 
Neuropsychiatric syndrome  1  0/91 (0.00%)  0/89 (0.00%)  1/88 (1.14%) 
Renal and urinary disorders       
Nephrolithiasis  1  0/91 (0.00%)  1/89 (1.12%)  1/88 (1.14%) 
Respiratory, thoracic and mediastinal disorders       
Pleural effusion  1  0/91 (0.00%)  0/89 (0.00%)  1/88 (1.14%) 
Vascular disorders       
Deep vein Thrombosis  1  1/91 (1.10%)  0/89 (0.00%)  0/88 (0.00%) 
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo RVT-101 35 mg RVT-101 70 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   66/91 (72.53%)   69/89 (77.53%)   59/88 (67.05%) 
Gastrointestinal disorders       
Constipation  1  5/91 (5.49%)  9/89 (10.11%)  6/88 (6.82%) 
Diarrhoea  1  3/91 (3.30%)  7/89 (7.87%)  5/88 (5.68%) 
Nausea  1  2/91 (2.20%)  4/89 (4.49%)  5/88 (5.68%) 
Infections and infestations       
Urinary tract infection  1  4/91 (4.40%)  7/89 (7.87%)  7/88 (7.95%) 
Upper respiratory tract infection  1  6/91 (6.59%)  3/89 (3.37%)  2/88 (2.27%) 
Injury, poisoning and procedural complications       
Fall  1  19/91 (20.88%)  17/89 (19.10%)  18/88 (20.45%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  0/91 (0.00%)  7/89 (7.87%)  5/88 (5.68%) 
Nervous system disorders       
Dizziness  1  4/91 (4.40%)  3/89 (3.37%)  5/88 (5.68%) 
Psychiatric disorders       
Hallucination, visual  1  4/91 (4.40%)  6/89 (6.74%)  3/88 (3.41%) 
Confusional state  1  3/91 (3.30%)  5/89 (5.62%)  5/88 (5.68%) 
Anxiety  1  3/91 (3.30%)  5/89 (5.62%)  2/88 (2.27%) 
Respiratory, thoracic and mediastinal disorders       
Nasopharygitis  1  7/91 (7.69%)  8/89 (8.99%)  1/88 (1.14%) 
Vascular disorders       
Orthostatic hypotension  1  12/91 (13.19%)  3/89 (3.37%)  5/88 (5.68%) 
Hypertension  1  5/91 (5.49%)  1/89 (1.12%)  2/88 (2.27%) 
1
Term from vocabulary, MedDRA 19.1
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.
All proposed manuscripts, publications or abstracts must be reviewed and approved by the Sponsor 60 days prior to submission for publication. All confidential information identified by the Sponsor must be deleted prior to submission.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Ilise Lombardo, MD
Organization: Axovant Sciences, Inc.
Phone: 646-822-8626
EMail: ilise.lombardo@axovant.com
Layout table for additonal information
Responsible Party: Axovant Sciences Ltd.
ClinicalTrials.gov Identifier: NCT02669433     History of Changes
Other Study ID Numbers: RVT-101-2001
First Submitted: January 25, 2016
First Posted: February 1, 2016
Results First Submitted: December 31, 2018
Results First Posted: April 26, 2019
Last Update Posted: April 26, 2019