Trial Outcomes & Findings for BTRX-246040 Administered Once Daily to Patients With Major Depressive Disorder (NCT NCT03193398)

NCT ID: NCT03193398

Last Updated: 2021-05-11

Results Overview

The Investigator-administered MADRS includes 10 items assessing the following symptoms: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (absence of symptom) to 6 (severe symptom); the overall score ranges from 0 to 60. MADRS total scores from 0 to 6 indicate normal/symptom absent, from 7 to 19 indicate mild depression, from 20 to 34 indicate moderate depression, and from 35 to 60 indicate severe depression.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

104 participants

Primary outcome timeframe

Week 8

Results posted on

2021-05-11

Participant Flow

Total of 104 subjects were randomized for the study NEP-MDD-201

Participant milestones

Participant milestones
Measure
BTRX-246040
40 mg administered orally as 1 capsule QD for 1 week, followed by 80 mg as 2 capsules QD for 7 weeks. BTRX-246040 oral capsule(s): BTRX-246040 administered once daily to patients with MDD for 8 weeks
Placebo
administered orally as 1 capsule QD for 1 week, followed by 2 capsules QD for 7 weeks. Placebo oral capsule(s): administered once daily to patients with MDD for 8 weeks
Overall Study
STARTED
53
51
Overall Study
COMPLETED
38
35
Overall Study
NOT COMPLETED
15
16

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

BTRX-246040 Administered Once Daily to Patients With Major Depressive Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
BTRX-246040
n=52 Participants
40 mg administered orally as 1 capsule QD for 1 week, followed by 80 mg as 2 capsules QD for 7 weeks. BTRX-246040 oral capsule(s): BTRX-246040 administered once daily to patients with MDD for 8 weeks
Placebo
n=50 Participants
administered orally as 1 capsule QD for 1 week, followed by 2 capsules QD for 7 weeks. Placebo oral capsule(s): administered once daily to patients with MDD for 8 weeks
Total
n=102 Participants
Total of all reporting groups
Age, Continuous
39.3 years
STANDARD_DEVIATION 12.29 • n=93 Participants
42.6 years
STANDARD_DEVIATION 15.00 • n=4 Participants
40.9 years
STANDARD_DEVIATION 13.72 • n=27 Participants
Sex: Female, Male
Female
11 Participants
n=93 Participants
13 Participants
n=4 Participants
24 Participants
n=27 Participants
Sex: Female, Male
Male
41 Participants
n=93 Participants
37 Participants
n=4 Participants
78 Participants
n=27 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
9 Participants
n=93 Participants
9 Participants
n=4 Participants
18 Participants
n=27 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
43 Participants
n=93 Participants
41 Participants
n=4 Participants
84 Participants
n=27 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
Race/Ethnicity, Customized
Asian
1 Participants
n=93 Participants
3 Participants
n=4 Participants
4 Participants
n=27 Participants
Race/Ethnicity, Customized
Black or African American
22 Participants
n=93 Participants
19 Participants
n=4 Participants
41 Participants
n=27 Participants
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islanders
0 Participants
n=93 Participants
1 Participants
n=4 Participants
1 Participants
n=27 Participants
Race/Ethnicity, Customized
White
24 Participants
n=93 Participants
26 Participants
n=4 Participants
50 Participants
n=27 Participants
Race/Ethnicity, Customized
Multiracial
5 Participants
n=93 Participants
1 Participants
n=4 Participants
6 Participants
n=27 Participants

PRIMARY outcome

Timeframe: Week 8

Population: The full analysis set (FAS) contained all patients in the randomized set who received at least 1 dose of study medication and had at least 1 post-dose efficacy assessment

The Investigator-administered MADRS includes 10 items assessing the following symptoms: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (absence of symptom) to 6 (severe symptom); the overall score ranges from 0 to 60. MADRS total scores from 0 to 6 indicate normal/symptom absent, from 7 to 19 indicate mild depression, from 20 to 34 indicate moderate depression, and from 35 to 60 indicate severe depression.

Outcome measures

Outcome measures
Measure
BTRX-246040
n=52 Participants
40 mg administered orally as 1 capsule QD for 1 week, followed by 80 mg as 2 capsules QD for 7 weeks. BTRX-246040 oral capsule(s): BTRX-246040 administered once daily to patients with MDD for 8 weeks
Placebo
n=50 Participants
administered orally as 1 capsule QD for 1 week, followed by 2 capsules QD for 7 weeks. Placebo oral capsule(s): administered once daily to patients with MDD for 8 weeks
Change in Investigator-administered MADRS Total Score From Baseline BTRX-246040 and Placebo
-15.0 Change in score on a scale from baseline
Standard Error 1.73
-13.6 Change in score on a scale from baseline
Standard Error 1.79

SECONDARY outcome

Timeframe: Week 8

Population: The full analysis set (FAS) contained all patients in the randomized set who received at least 1 dose of study medication and had at least 1 post-dose efficacy assessment

The Investigator-administered MADRS-6 subscale focuses on the core symptoms of depression and assesses the following symptoms: apparent sadness, reported sadness, inner tension, lassitude, inability to feel, and pessimistic thoughts. Each item is scored from 0 (absence of symptom) to 6 (severe symptom); the overall score ranges from 0 to 36. The change from baseline in the Investigator-administered MADRS-6 subscale was analyzed using the same method as the MADRS efficacy endpoint, substituting the baseline MADRS-6 subscale as the covariate in place of the MADRS total score.

Outcome measures

Outcome measures
Measure
BTRX-246040
n=52 Participants
40 mg administered orally as 1 capsule QD for 1 week, followed by 80 mg as 2 capsules QD for 7 weeks. BTRX-246040 oral capsule(s): BTRX-246040 administered once daily to patients with MDD for 8 weeks
Placebo
n=50 Participants
administered orally as 1 capsule QD for 1 week, followed by 2 capsules QD for 7 weeks. Placebo oral capsule(s): administered once daily to patients with MDD for 8 weeks
Change From Baseline in Investigator-administered MADRS-6 Total Score
-10.7 Change in score on a scale from baseline
Standard Error 1.17
-9.7 Change in score on a scale from baseline
Standard Error 1.21

SECONDARY outcome

Timeframe: Week 8

Population: The full analysis set (FAS) contained all patients in the randomized set who received at least 1 dose of study medication and had at least 1 post-dose efficacy assessment

The Investigator-administered Hospital Anxiety and Depression Scale (HADS) subscales comprises of 7 questions regarding Depression and 7 questions regarding Anxiety. Each question is rated on a scale from 0 - 3. The outcome of the HADS questionnaire is two total scores, the HADS-A (for anxiety) and the HADS-D (for depression). Both total scores are graded on a scale of 0 - 21 and can be categorized as Normal (0 - 7), Borderline Abnormal (8 - 10) and Abnormal (11 - 21). Higher scores indicate higher levels of anxiety and depression.

Outcome measures

Outcome measures
Measure
BTRX-246040
n=52 Participants
40 mg administered orally as 1 capsule QD for 1 week, followed by 80 mg as 2 capsules QD for 7 weeks. BTRX-246040 oral capsule(s): BTRX-246040 administered once daily to patients with MDD for 8 weeks
Placebo
n=50 Participants
administered orally as 1 capsule QD for 1 week, followed by 2 capsules QD for 7 weeks. Placebo oral capsule(s): administered once daily to patients with MDD for 8 weeks
Change From Baseline in Investigator-administered HADS-A (Hospital Anxiety and Depression Scale - Anxiety Subscale) Score
-2.6 Change in score on a scale from baseline
Standard Error 0.67
-3.5 Change in score on a scale from baseline
Standard Error 0.70

SECONDARY outcome

Timeframe: Week 8

Population: The full analysis set (FAS) contained all patients in the randomized set who received at least 1 dose of study medication and had at least 1 post-dose efficacy assessment

The Investigator-administered Hospital Anxiety and Depression Scale (HADS) subscales comprises of 7 questions regarding Depression and 7 questions regarding Anxiety. Each question is rated on a scale from 0 - 3. The outcome of the HADS questionnaire is two total scores, the HADS-A (for anxiety) and the HADS-D (for depression). Both total scores are graded on a scale of 0 - 21 and can be categorized as Normal (0 - 7), Borderline Abnormal (8 - 10) and Abnormal (11 - 21). Higher scores indicate higher levels of anxiety and depression.

Outcome measures

Outcome measures
Measure
BTRX-246040
n=52 Participants
40 mg administered orally as 1 capsule QD for 1 week, followed by 80 mg as 2 capsules QD for 7 weeks. BTRX-246040 oral capsule(s): BTRX-246040 administered once daily to patients with MDD for 8 weeks
Placebo
n=50 Participants
administered orally as 1 capsule QD for 1 week, followed by 2 capsules QD for 7 weeks. Placebo oral capsule(s): administered once daily to patients with MDD for 8 weeks
Change From Baseline in Investigator-administered HADS-D (Hospital Anxiety and Depression Scale - Depression Subscale) Score
-5.0 Change in score on a scale from baseline
Standard Error 0.76
-5.9 Change in score on a scale from baseline
Standard Error 0.80

SECONDARY outcome

Timeframe: Week 8

Population: The full analysis set (FAS) contained all patients in the randomized set who received at least 1 dose of study medication and had at least 1 post-dose efficacy assessment

The Investigator-administered Dimensional Anhedonia Rating Scale (DARS) is a 17-item questionnaire with each answer between 0 and 4 on a Likert scale grading (0=Not at all, 1=Slightly, 2=Moderately, 3=Mostly, 4=Very Much). Therefore, the DARS total score is on a scale of 0 - 68. The DARS Total score is broken down into four dimensions; Hobbies, Food/Drink, Social Activities and Sensory Experience.

Outcome measures

Outcome measures
Measure
BTRX-246040
n=52 Participants
40 mg administered orally as 1 capsule QD for 1 week, followed by 80 mg as 2 capsules QD for 7 weeks. BTRX-246040 oral capsule(s): BTRX-246040 administered once daily to patients with MDD for 8 weeks
Placebo
n=50 Participants
administered orally as 1 capsule QD for 1 week, followed by 2 capsules QD for 7 weeks. Placebo oral capsule(s): administered once daily to patients with MDD for 8 weeks
Change From Baseline in Investigator-administered Dimensional Anhedonia Rating Scale (DARS)
13.7 Change in score on a scale from baseline
Standard Error 16.7
2.91 Change in score on a scale from baseline
Standard Error 3.04

SECONDARY outcome

Timeframe: Week 8

Population: The full analysis set (FAS) contained all patients in the randomized set who received at least 1 dose of study medication and had at least 1 post-dose efficacy assessment

The Investigator-administered Snaith Hamilton Pleasure Scale (SHAPS) is a 14-item questionnaire. The SHAPS is scored two different ways. Under the original scoring method, each question has 4 responses, 2 of which imply agreement (Definitely Agree, Agree; each scored as 0) and 2 which imply disagreement (Disagree, Strongly Disagree; each scored as 1). Therefore, the SHAPS total score ranges 0 - 14. In this study, in addition to the traditional scoring method, an alternative scoring method will assign 1 - Strongly Agree, 2 - Agree, 3 - Disagree, and 4 - Strongly Disagree. Using this alternative scoring method, the total score ranges 14-56. In both scoring systems, higher scores indicate greater anhedonia.

Outcome measures

Outcome measures
Measure
BTRX-246040
n=52 Participants
40 mg administered orally as 1 capsule QD for 1 week, followed by 80 mg as 2 capsules QD for 7 weeks. BTRX-246040 oral capsule(s): BTRX-246040 administered once daily to patients with MDD for 8 weeks
Placebo
n=50 Participants
administered orally as 1 capsule QD for 1 week, followed by 2 capsules QD for 7 weeks. Placebo oral capsule(s): administered once daily to patients with MDD for 8 weeks
Change From Baseline in Investigator-administered Snaith-Hamilton Pleasure Scale (SHAPS) Score
-6.7 Change in score on a scale from baseline
Standard Error 1.24
-7.9 Change in score on a scale from baseline
Standard Error 1.28

Adverse Events

BTRX-246040

Serious events: 0 serious events
Other events: 34 other events
Deaths: 0 deaths

Placebo

Serious events: 1 serious events
Other events: 27 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
BTRX-246040
n=53 participants at risk
40 mg administered orally as 1 capsule QD for 1 week, followed by 80 mg as 2 capsules QD for 7 weeks. BTRX-246040 oral capsule(s): BTRX-246040 administered once daily to patients with MDD for 8 weeks
Placebo
n=51 participants at risk
administered orally as 1 capsule QD for 1 week, followed by 2 capsules QD for 7 weeks. Placebo oral capsule(s): administered once daily to patients with MDD for 8 weeks
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10

Other adverse events

Other adverse events
Measure
BTRX-246040
n=53 participants at risk
40 mg administered orally as 1 capsule QD for 1 week, followed by 80 mg as 2 capsules QD for 7 weeks. BTRX-246040 oral capsule(s): BTRX-246040 administered once daily to patients with MDD for 8 weeks
Placebo
n=51 participants at risk
administered orally as 1 capsule QD for 1 week, followed by 2 capsules QD for 7 weeks. Placebo oral capsule(s): administered once daily to patients with MDD for 8 weeks
Nervous system disorders
Headache
15.1%
8/53 • Up to week 10
25.5%
13/51 • Up to week 10
Nervous system disorders
Somnolence
5.7%
3/53 • Up to week 10
13.7%
7/51 • Up to week 10
Nervous system disorders
Dizziness
1.9%
1/53 • Up to week 10
3.9%
2/51 • Up to week 10
Nervous system disorders
Paraesthesia
3.8%
2/53 • Up to week 10
0.00%
0/51 • Up to week 10
Nervous system disorders
Disturbance In Attention
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Nervous system disorders
Formication
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Nervous system disorders
Hypogeusia
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10
Nervous system disorders
Sedation
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Infections and infestations
Upper Respiratory Tract Infection
5.7%
3/53 • Up to week 10
3.9%
2/51 • Up to week 10
Infections and infestations
Gastroenteritis
5.7%
3/53 • Up to week 10
2.0%
1/51 • Up to week 10
Infections and infestations
Urinary Tract Infection
5.7%
3/53 • Up to week 10
2.0%
1/51 • Up to week 10
Infections and infestations
Influenza
0.00%
0/53 • Up to week 10
3.9%
2/51 • Up to week 10
Infections and infestations
Dermatitis Infected
0.00%
0/53 • Up to week 10
3.9%
2/51 • Up to week 10
Infections and infestations
Pharyngitis
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10
Infections and infestations
Skin Infection
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10
Infections and infestations
Tooth Infection
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Infections and infestations
Viral Upper Respiratory Tract Infection
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10
Infections and infestations
Vulvovaginal Mycotic Infection
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Gastrointestinal disorders
Nausea
9.4%
5/53 • Up to week 10
5.9%
3/51 • Up to week 10
Gastrointestinal disorders
Diarrhoea
3.8%
2/53 • Up to week 10
2.0%
1/51 • Up to week 10
Gastrointestinal disorders
Abdominal Pain
3.8%
2/53 • Up to week 10
2.0%
1/51 • Up to week 10
Gastrointestinal disorders
Abdominal Pain Upper
1.9%
1/53 • Up to week 10
2.0%
1/51 • Up to week 10
Gastrointestinal disorders
Constipation
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Gastrointestinal disorders
Dyspepsia
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10
Gastrointestinal disorders
Food Poisoning
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10
Gastrointestinal disorders
Toothache
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10
Gastrointestinal disorders
Vomiting
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10
Psychiatric disorders
Anxiety
5.7%
3/53 • Up to week 10
2.0%
1/51 • Up to week 10
Psychiatric disorders
Irritability
5.7%
3/53 • Up to week 10
2.0%
1/51 • Up to week 10
Psychiatric disorders
Insomnia
1.9%
1/53 • Up to week 10
2.0%
1/51 • Up to week 10
Psychiatric disorders
Restlessness
3.8%
2/53 • Up to week 10
0.00%
0/51 • Up to week 10
Psychiatric disorders
Abnormal Dreams
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Psychiatric disorders
Suicidal Ideation
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10
Musculoskeletal and connective tissue disorders
Myalgia
1.9%
1/53 • Up to week 10
3.9%
2/51 • Up to week 10
Musculoskeletal and connective tissue disorders
Back Pain
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Musculoskeletal and connective tissue disorders
Intervertebral Disc Protrusion
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10
Musculoskeletal and connective tissue disorders
Muscle Spasms
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10
Musculoskeletal and connective tissue disorders
Muscle Tightness
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10
Musculoskeletal and connective tissue disorders
Muscle Twitching
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10
Musculoskeletal and connective tissue disorders
Neck Pain
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10
Musculoskeletal and connective tissue disorders
Pain In Extremity
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Injury, poisoning and procedural complications
Contusion
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Injury, poisoning and procedural complications
Laceration
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Injury, poisoning and procedural complications
Ligament Rupture
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Injury, poisoning and procedural complications
Muscle Strain
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Injury, poisoning and procedural complications
Procedural Pain
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Injury, poisoning and procedural complications
Road Traffic Accident
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Injury, poisoning and procedural complications
Skin Abrasion
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Investigations
Alanine Aminotransferase Increased
0.00%
0/53 • Up to week 10
3.9%
2/51 • Up to week 10
Investigations
Aspartate Aminotransferase Increased
0.00%
0/53 • Up to week 10
3.9%
2/51 • Up to week 10
Investigations
Blood Creatine Phosphokinase Increased
0.00%
0/53 • Up to week 10
3.9%
2/51 • Up to week 10
Investigations
Amylase Increased
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Investigations
Lipase Increased
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Investigations
Weight Increased
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10
General disorders
Non-Cardiac Chest Pain
1.9%
1/53 • Up to week 10
2.0%
1/51 • Up to week 10
General disorders
Fatigue
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10
General disorders
Influenza Like Illness
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Eye disorders
Vision Blurred
3.8%
2/53 • Up to week 10
0.00%
0/51 • Up to week 10
Eye disorders
Eyelid Oedema
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Eye disorders
Lacrimation Increased
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Respiratory, thoracic and mediastinal disorders
Epistaxis
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Respiratory, thoracic and mediastinal disorders
Throat Irritation
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10
Skin and subcutaneous tissue disorders
Acne
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10
Skin and subcutaneous tissue disorders
Pruritus Generalised
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10
Blood and lymphatic system disorders
Benign Ethnic Neutropenia
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10
Cardiac disorders
Tachycardia
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10
Ear and labyrinth disorders
Ear Discomfort
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Metabolism and nutrition disorders
Decreased Appetite
0.00%
0/53 • Up to week 10
2.0%
1/51 • Up to week 10
Vascular disorders
Hot Flush
1.9%
1/53 • Up to week 10
0.00%
0/51 • Up to week 10

Additional Information

Jane Tiller, MD; Study Director

BlackThorn Therapeutics, Inc.

Phone: (415) 548-5313

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place