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Phase 3 Study of Intranasal Carbetocin (LV-101) in Patients With Prader-Willi Syndrome (CARE-PWS)

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: NCT03649477
Recruitment Status : Active, not recruiting
First Posted : August 28, 2018
Results First Posted : November 17, 2021
Last Update Posted : November 17, 2021
Sponsor:
Information provided by (Responsible Party):
Levo Therapeutics, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Prader-Willi Syndrome
Interventions Drug: 3.2 mg intranasal carbetocin
Drug: 9.6 mg intranasal carbetocin
Drug: placebo
Enrollment 130
Recruitment Details Participants were enrolled in three countries, the United States, Canada and Australia. The first participant was screened in November 2018, the first participant was enrolled in December 2018, and the last participant was enrolled in March 2020.
Pre-assignment Details Subjects were randomized 1:1:1 at Baseline to receive the 9.6 mg/dose, 3.2 mg/dose, or placebo during the 8-week placebo-controlled period. A total of 130 subjects were evaluated (44 subjects in the 9.6 mg/dose arm, and 43 subjects each in the 3.2 mg/dose and placebo arms). Of these 130 subjects, 128 subjects (98.5%) completed the Week 8 visit and entered into the long-term follow-up period.
Arm/Group Title 9.6 mg of LV-101 3.2 mg of LV-101 Placebo
Hide Arm/Group Description

9.6 mg of LV-101 during the 8-week placebo-controlled period

9.6 mg intranasal carbetocin: three times per day with meals

3.2 mg of LV-101 during the 8-week placebo controlled period

3.2 mg intranasal carbetocin: three times per day with meals

Matched intranasal placebo during the 8-week placebo controlled period

placebo: three times per day with meals

Period Title: Overall Study
Started 44 43 43
Completed 42 43 43
Not Completed 2 0 0
Reason Not Completed
Adverse Event             2             0             0
Arm/Group Title 9.6 mg of LV-101 3.2 mg of LV-101 Placebo Total
Hide Arm/Group Description

9.6 mg of LV-101 during the 8-week placebo-controlled period

9.6 mg intranasal carbetocin: three times per day with meals

3.2 mg of LV-101 during the 8-week placebo controlled period

3.2 mg intranasal carbetocin: three times per day with meals

Matched intranasal placebo during the 8-week placebo controlled period

placebo: three times per day with meals

Total of all reporting groups
Overall Number of Baseline Participants 44 43 43 130
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 43 participants 43 participants 130 participants
<=18 years
42
  95.5%
43
 100.0%
43
 100.0%
128
  98.5%
Between 18 and 65 years
2
   4.5%
0
   0.0%
0
   0.0%
2
   1.5%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Description: Inclusion criteria was 7 to 18 years of age at Screening. Subjects who were 19 years of age at Baseline were still eligible to participate if all other eligibility criteria were met.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 43 participants 43 participants 130 participants
Female
21
  47.7%
27
  62.8%
24
  55.8%
72
  55.4%
Male
23
  52.3%
16
  37.2%
19
  44.2%
58
  44.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 43 participants 43 participants 130 participants
Hispanic or Latino
4
   9.1%
5
  11.6%
4
   9.3%
13
  10.0%
Not Hispanic or Latino
40
  90.9%
38
  88.4%
39
  90.7%
117
  90.0%
Unknown or Not Reported
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 44 participants 43 participants 43 participants 130 participants
American Indian or Alaska Native
1
   2.3%
0
   0.0%
0
   0.0%
1
   0.8%
Asian
2
   4.5%
2
   4.7%
1
   2.3%
5
   3.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   2.3%
2
   4.7%
1
   2.3%
4
   3.1%
White
37
  84.1%
37
  86.0%
37
  86.0%
111
  85.4%
More than one race
3
   6.8%
2
   4.7%
4
   9.3%
9
   6.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Hyperphagia Behavior
Hide Description

Change in hyperphagia (extreme hunger) as measured by the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Total Score versus placebo.

Score range: 0-36; higher scores mean a worse outcome. Reduction in score indicates improvement.

Time Frame Baseline to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: A subset of the Full Analysis Set that included all subjects with at least one post-Baseline visit (i.e., Week 2 or Week 8) completed prior to March 01, 2020 and excluded all efficacy data collected on or after March 01, 2020.
Arm/Group Title 9.6 mg of LV-101 3.2 mg of LV-101 Placebo
Hide Arm/Group Description:

9.6 mg of LV-101 during the 8-week placebo-controlled period

9.6 mg intranasal carbetocin: three times per day with meals

3.2 mg of LV-101 during the 8-week placebo controlled period

3.2 mg intranasal carbetocin: three times per day with meals

Matched intranasal placebo during the 8-week placebo controlled period

placebo: three times per day with meals

Overall Number of Participants Analyzed 40 39 40
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
-3.439
(-5.304 to -1.575)
-5.372
(-7.259 to -3.486)
-2.237
(-4.095 to -0.378)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 9.6 mg of LV-101, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3493
Comments 0.05 threshold for statistical significance
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.202
Confidence Interval (2-Sided) 95%
-3.729 to 1.324
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 3.2 mg of LV-101, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0162
Comments 0.05 threshold for statistical significance
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.136
Confidence Interval (2-Sided) 95%
-5.685 to -0.586
Estimation Comments [Not Specified]
2.Primary Outcome
Title Obsessive and Compulsive Behaviors
Hide Description

Change in obsessive and compulsive behaviors as measured by the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) Total Score versus placebo.

Score range: 0-40; higher scores mean a worse outcome. Reduction in score indicates improvement.

Time Frame baseline to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: A subset of the Full Analysis Set that included all subjects with at least one post-Baseline visit (i.e., Week 2 or Week 8) completed prior to March 01, 2020 and excluded all efficacy data collected on or after March 01, 2020.
Arm/Group Title 9.6 mg of LV-101 3.2 mg of LV-101 Placebo
Hide Arm/Group Description:

9.6 mg of LV-101 during the 8-week placebo-controlled period

9.6 mg intranasal carbetocin: three times per day with meals

3.2 mg of LV-101 during the 8-week placebo controlled period

3.2 mg intranasal carbetocin: three times per day with meals

Matched intranasal placebo during the 8-week placebo controlled period

placebo: three times per day with meals

Overall Number of Participants Analyzed 40 39 40
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
-2.968
(-4.667 to -1.268)
-3.123
(-4.843 to -1.403)
-2.360
(-4.046 to -0.674)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 9.6 mg of LV-101, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6001
Comments 0.05 threshold for statistical significance
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.608
Confidence Interval (2-Sided) 95%
-2.890 to 1.674
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 3.2 mg of LV-101, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5143
Comments 0.05 threshold for statistical significance
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.764
Confidence Interval (2-Sided) 95%
-3.068 to 1.541
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Anxiety
Hide Description

Change in participant anxiety as measured by the PWS Anxiety and Distress Questionnaire (PADQ) Total Score versus placebo.

Score range: 0-56; higher scores mean a worse outcome. Reduction in score indicates improvement.

Time Frame Baseline to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: A subset of the Full Analysis Set that included all subjects with at least one post-Baseline visit (i.e., Week 2 or Week 8) completed prior to March 01, 2020 and excluded all efficacy data collected on or after March 01, 2020.
Arm/Group Title 9.6 mg of LV-101 3.2 mg of LV-101 Placebo
Hide Arm/Group Description:

9.6 mg of LV-101 during the 8-week placebo-controlled period

9.6 mg intranasal carbetocin: three times per day with meals

3.2 mg of LV-101 during the 8-week placebo controlled period

3.2 mg intranasal carbetocin: three times per day with meals

Matched intranasal placebo during the 8-week placebo controlled period

placebo: three times per day with meals

Overall Number of Participants Analyzed 40 39 40
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
-4.306
(-6.797 to -1.815)
-8.301
(-10.790 to -5.811)
-4.489
(-6.942 to -2.037)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 9.6 mg of LV-101, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9144
Comments 0.05 threshold for statistical significance
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.183
Confidence Interval (2-Sided) 95%
-3.175 to 3.541
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 3.2 mg of LV-101, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0266
Comments 0.05 threshold for statistical significance
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.812
Confidence Interval (2-Sided) 95%
-7.177 to -0.446
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Global Impression
Hide Description Clinical Global Impression of Change (CGI-C) score versus placebo. Score range: 1-7; higher scores mean a worse outcome. Reduction in score indicates improvement.
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: A subset of the Full Analysis Set that included all subjects with at least one post-Baseline visit (i.e., Week 2 or Week 8) completed prior to March 01, 2020 and excluded all efficacy data collected on or after March 01, 2020.
Arm/Group Title 9.6 mg of LV-101 3.2 mg of LV-101 Placebo
Hide Arm/Group Description:

9.6 mg of LV-101 during the 8-week placebo-controlled period

9.6 mg intranasal carbetocin: three times per day with meals

3.2 mg of LV-101 during the 8-week placebo controlled period

3.2 mg intranasal carbetocin: three times per day with meals

Matched intranasal placebo during the 8-week placebo controlled period

placebo: three times per day with meals

Overall Number of Participants Analyzed 40 39 40
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
3.582
(3.250 to 3.913)
3.395
(3.057 to 3.733)
3.893
(3.562 to 4.225)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 9.6 mg of LV-101, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1598
Comments 0.05 threshold for statistical significance
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.312
Confidence Interval (2-Sided) 95%
-0.748 to 0.125
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 3.2 mg of LV-101, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0266
Comments 0.05 threshold for statistical significance
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.498
Confidence Interval (2-Sided) 95%
-0.937 to -0.059
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Hyperphagia Behavior (Subset)
Hide Description

Change in hyperphagia as measured by the change in specified subsets of HQ-CT questions versus placebo.

Score range: 0-24; higher scores mean a worse outcome. Reduction in score indicates improvement.

Time Frame Baseline to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: A subset of the Full Analysis Set that included all subjects with at least one post-Baseline visit (i.e., Week 2 or Week 8) completed prior to March 01, 2020 and excluded all efficacy data collected on or after March 01, 2020.
Arm/Group Title 9.6 mg of LV-101 3.2 mg of LV-101 Placebo
Hide Arm/Group Description:

9.6 mg of LV-101 during the 8-week placebo-controlled period

9.6 mg intranasal carbetocin: three times per day with meals

3.2 mg of LV-101 during the 8-week placebo controlled period

3.2 mg intranasal carbetocin: three times per day with meals

Matched intranasal placebo during the 8-week placebo controlled period

placebo: three times per day with meals

Overall Number of Participants Analyzed 40 39 40
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
-3.295
(-4.667 to -1.922)
-4.621
(-6.010 to -3.233)
-2.209
(-3.577 to -0.841)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 9.6 mg of LV-101, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2479
Comments 0.05 threshold for statistical significance
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.085
Confidence Interval (2-Sided) 95%
-2.932 to 0.761
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 3.2 mg of LV-101, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0114
Comments 0.05 for statistical significance
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.412
Confidence Interval (2-Sided) 95%
-4.276 to -0.548
Estimation Comments [Not Specified]
Time Frame 8-week placebo-controlled period
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 9.6 mg of LV-101 3.2 mg of LV-101 Placebo
Hide Arm/Group Description

9.6 mg of LV-101 during the 8-week placebo controlled period

9.6 mg intranasal carbetocin: three times per day with meals

3.2 mg of LV-101 during the 8-weeks placebo-controlled period

3.2 mg intranasal carbetocin: three times per day with meals

Matched intranasal placebo during 8-week placebo-controlled period

placebo: three times per day with meals

All-Cause Mortality
9.6 mg of LV-101 3.2 mg of LV-101 Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/44 (0.00%)      0/43 (0.00%)      0/43 (0.00%)    
Hide Serious Adverse Events
9.6 mg of LV-101 3.2 mg of LV-101 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/44 (0.00%)      0/43 (0.00%)      0/43 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
9.6 mg of LV-101 3.2 mg of LV-101 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   20/44 (45.45%)      19/43 (44.19%)      10/43 (23.26%)    
Gastrointestinal disorders       
Diarrhea  1  2/44 (4.55%)  2 4/43 (9.30%)  5 1/43 (2.33%)  1
General disorders       
Pyrexia  1  0/44 (0.00%)  0 3/43 (6.98%)  3 0/43 (0.00%)  0
Upper respiratory tract infection  1  2/44 (4.55%)  2 3/43 (6.98%)  4 2/43 (4.65%)  2
Infections and infestations       
Nasopharyngitis  1  1/44 (2.27%)  1 0/43 (0.00%)  0 3/43 (6.98%)  3
Nervous system disorders       
Headache  1  4/44 (9.09%)  4 7/43 (16.28%)  8 3/43 (6.98%)  6
Respiratory, thoracic and mediastinal disorders       
Epistaxis  1  6/44 (13.64%)  7 1/43 (2.33%)  2 1/43 (2.33%)  2
Nasal discomfort  1  2/44 (4.55%)  2 3/43 (6.98%)  3 1/43 (2.33%)  1
Vascular disorders       
Flushing  1  9/44 (20.45%)  10 6/43 (13.95%)  6 0/43 (0.00%)  0
1
Term from vocabulary, MedDRA 23.0
Indicates events were collected by systematic assessment
The COVID-19 pandemic began affecting this study in early March 2020 by substantially impacting the ability to safely enroll clinical study subjects, by requiring remote visits and monitoring, and by dramatically changing daily routines and social environments in this sensitive PWS population. Levo held new screening and enrollment in March 2020, and subsequently closed screening and enrollment in May 2020, resulting in the enrollment of 130 subjects instead of the 175 subjects planned.
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.
This study is a multi-center study. Sponsor retains first publication rights for a period of time after conclusion of study. Study has not yet completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Vice President of Clinical Development
Organization: Levo Therapeutics
Phone: 1-847-901-9260
EMail: contactus@levotx.com
Layout table for additonal information
Responsible Party: Levo Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03649477    
Other Study ID Numbers: LV-101-3-01
First Submitted: August 24, 2018
First Posted: August 28, 2018
Results First Submitted: August 30, 2021
Results First Posted: November 17, 2021
Last Update Posted: November 17, 2021