Trial Outcomes & Findings for Clinical Trial of Efficacy and Safety of Rengalin in the Treatment of Cough in Patients With Chronic Obstructive Pulmonary Disease (NCT NCT03159091)

Last Updated: 2020-12-11

Results Overview

Cough Severity Scale (CSS) total score. Cough intensity according to the scale is assessed in daytime and at night in points where 0 - no cough, 5 - continuous exhausting cough in daytime and at night. Response criterion: ≥1 lower total CSS score compared to baseline.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

238 participants

Primary outcome timeframe

in 4 weeks of the treatment

Results posted on

2020-12-11

Participant Flow

Participant milestones

Participant milestones
Measure	Rengalin Oral administration. Two tablets per intake. The tablet should be held in the mouth until complete dissolution. 2 tablets 3 times a day without food (i.e. 15-30 min prior to meal or 15-30 min after meal). Rengalin: Oral administration.	Placebo Oral administration. Two tablets per intake. The tablet should be held in the mouth until complete dissolution. 2 tablets 3 times a day without food (i.e. 15-30 min prior to meal or 15-30 min after meal). Placebo: Oral administration.
Overall Study STARTED	121	117
Overall Study COMPLETED	116	113
Overall Study NOT COMPLETED	5	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Rengalin Oral administration. Two tablets per intake. The tablet should be held in the mouth until complete dissolution. 2 tablets 3 times a day without food (i.e. 15-30 min prior to meal or 15-30 min after meal). Rengalin: Oral administration.	Placebo Oral administration. Two tablets per intake. The tablet should be held in the mouth until complete dissolution. 2 tablets 3 times a day without food (i.e. 15-30 min prior to meal or 15-30 min after meal). Placebo: Oral administration.
Overall Study Incorrect inclusion ineligible patient	5	3
Overall Study Patient has taken no dose of study drug	0	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rengalin n=121 Participants Oral administration. Two tablets per intake. The tablet should be held in the mouth until complete dissolution. 2 tablets 3 times a day without food (i.e. 15-30 min prior to meal or 15-30 min after meal). Rengalin: Oral administration.	Placebo n=117 Participants Oral administration. Two tablets per intake. The tablet should be held in the mouth until complete dissolution. 2 tablets 3 times a day without food (i.e. 15-30 min prior to meal or 15-30 min after meal). Placebo: Oral administration.	Total n=238 Participants Total of all reporting groups
Age, Continuous	63.9 years STANDARD_DEVIATION 7.9 • n=121 Participants	64.8 years STANDARD_DEVIATION 8.4 • n=117 Participants	64.3 years STANDARD_DEVIATION 8.2 • n=238 Participants
Sex: Female, Male Female	27 Participants n=121 Participants	23 Participants n=117 Participants	50 Participants n=238 Participants
Sex: Female, Male Male	94 Participants n=121 Participants	94 Participants n=117 Participants	188 Participants n=238 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Russia	121 Participants n=121 Participants	117 Participants n=117 Participants	238 Participants n=238 Participants

PRIMARY outcome

Timeframe: in 4 weeks of the treatment

Outcome measures

Outcome measures
Measure	Rengalin n=116 Participants Oral administration. Two tablets per intake. The tablet should be held in the mouth until complete dissolution. 2 tablets 3 times a day without food (i.e. 15-30 min prior to meal or 15-30 min after meal). Rengalin: Oral administration.	Placebo n=113 Participants Oral administration. Two tablets per intake. The tablet should be held in the mouth until complete dissolution. 2 tablets 3 times a day without food (i.e. 15-30 min prior to meal or 15-30 min after meal). Placebo: Oral administration.
Percentage of Patients With a Positive Treatment Response	97 Participants	82 Participants

SECONDARY outcome

Timeframe: Baseline and 4 weeks after the treatment

Cough Severity Scale (CSS) total score. Cough intensity according to the scale is assessed in the daytime and at night in points, where 0 - no cough, 5 - continuous exhausting cough in the daytime, and at night.

Outcome measures

Outcome measures
Measure	Rengalin n=116 Participants Oral administration. Two tablets per intake. The tablet should be held in the mouth until complete dissolution. 2 tablets 3 times a day without food (i.e. 15-30 min prior to meal or 15-30 min after meal). Rengalin: Oral administration.	Placebo n=113 Participants Oral administration. Two tablets per intake. The tablet should be held in the mouth until complete dissolution. 2 tablets 3 times a day without food (i.e. 15-30 min prior to meal or 15-30 min after meal). Placebo: Oral administration.
Severity of Cough After 4 Weeks Compared to Baseline Initial total score	4.18 score on a scale Standard Deviation 1.42	4.12 score on a scale Standard Deviation 1.42
Severity of Cough After 4 Weeks Compared to Baseline Total score after 4 weeks	2.56 score on a scale Standard Deviation 1.35	2.78 score on a scale Standard Deviation 1.16
Severity of Cough After 4 Weeks Compared to Baseline ∆ between initial and 4 weeks total scores	1.62 score on a scale Standard Deviation 1.38	1.35 score on a scale Standard Deviation 1.20

SECONDARY outcome

Timeframe: in 4 weeks of the treatment

Number of Participants with a Decrease from Baseline of ≥50% in Cough Severity at 4 weeks. Based on the total Cough Severity Scale (CSS) score. Cough intensity according to the scale is assessed in the daytime and at night in points, where 0 - no cough, 5 - continuous exhausting cough in the daytime and at night.

Outcome measures

Outcome measures
Measure	Rengalin n=116 Participants Oral administration. Two tablets per intake. The tablet should be held in the mouth until complete dissolution. 2 tablets 3 times a day without food (i.e. 15-30 min prior to meal or 15-30 min after meal). Rengalin: Oral administration.	Placebo n=113 Participants Oral administration. Two tablets per intake. The tablet should be held in the mouth until complete dissolution. 2 tablets 3 times a day without food (i.e. 15-30 min prior to meal or 15-30 min after meal). Placebo: Oral administration.
Percentage of Patients With ≥50% Lesser Cough Severity at 4 Weeks	49 Participants	37 Participants

SECONDARY outcome

Timeframe: in 4 weeks of the treatment

Based on the total COPD Assessment Test (CAT) score. CAT consists of 8 items. Each item ranges from "0" to "5" balls. The total score ranges from minimum "0" to maximum "40" points. Higher values represent a worse outcome.

Outcome measures

Outcome measures
Measure	Rengalin n=116 Participants Oral administration. Two tablets per intake. The tablet should be held in the mouth until complete dissolution. 2 tablets 3 times a day without food (i.e. 15-30 min prior to meal or 15-30 min after meal). Rengalin: Oral administration.	Placebo n=113 Participants Oral administration. Two tablets per intake. The tablet should be held in the mouth until complete dissolution. 2 tablets 3 times a day without food (i.e. 15-30 min prior to meal or 15-30 min after meal). Placebo: Oral administration.
Changes in Clinical Symptoms of Chronic Obstructive Pulmonary Disease (COPD) Initial total score	19.9 score on a scale Standard Deviation 6.8	20.3 score on a scale Standard Deviation 6.6
Changes in Clinical Symptoms of Chronic Obstructive Pulmonary Disease (COPD) Total score after 4 weeks	16.6 score on a scale Standard Deviation 6.9	17.8 score on a scale Standard Deviation 6.8
Changes in Clinical Symptoms of Chronic Obstructive Pulmonary Disease (COPD) ∆ between initial and 4 weeks total scores	3.3 score on a scale Standard Deviation 4.2	2.5 score on a scale Standard Deviation 4.1

SECONDARY outcome

Timeframe: in 4 weeks of the treatment

COPD exacerbation is defined as an acute event characterized by aggravation of the event within 2-3 or more days. Exacerbation manifests in intensification of respiratory disorders beyond their regular daily fluctuations and require administration of products in addition to the previously prescribed basic therapy as well as a rescue drug for symptom relief (salbutamol). Additional products include antibacterial drugs, systemic corticosteroids and/or emergency therapy (ambulance call) or hospitalization for COPD exacerbation. COPD exacerbation is recorded as an adverse event. If a COPD exacerbation develops within the first week of the subject participation in the study, it will not be considered as a secondary inefficacy criterion

Outcome measures

Outcome measures
Measure	Rengalin n=116 Participants Oral administration. Two tablets per intake. The tablet should be held in the mouth until complete dissolution. 2 tablets 3 times a day without food (i.e. 15-30 min prior to meal or 15-30 min after meal). Rengalin: Oral administration.	Placebo n=113 Participants Oral administration. Two tablets per intake. The tablet should be held in the mouth until complete dissolution. 2 tablets 3 times a day without food (i.e. 15-30 min prior to meal or 15-30 min after meal). Placebo: Oral administration.
Percentage of Patients With no Exacerbation of COPD	115 Participants	113 Participants

Adverse Events

Rengalin

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 11 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Rengalin n=121 participants at risk Oral administration. Two tablets per intake. The tablet should be held in the mouth until complete dissolution. 2 tablets 3 times a day without food (i.e. 15-30 min prior to meal or 15-30 min after meal). Rengalin: Oral administration.	Placebo n=116 participants at risk Oral administration. Two tablets per intake. The tablet should be held in the mouth until complete dissolution. 2 tablets 3 times a day without food (i.e. 15-30 min prior to meal or 15-30 min after meal). Placebo: Oral administration.
Infections and infestations Influenza A (H1N1)	0.83% 1/121 • Number of events 1 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).	0.00% 0/116 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).
Respiratory, thoracic and mediastinal disorders COPD exacerbation	0.83% 1/121 • Number of events 1 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).	0.00% 0/116 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).
Cardiac disorders Myocardial infarction	0.00% 0/121 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).	0.86% 1/116 • Number of events 1 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).

Other adverse events

Additional Information

Mikhail Putilovskiy, MD, PhD, Clinical and Medical Department Director

Materia Medica Holding

Phone: +74952761571

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Rengalin n=121 participants at risk Oral administration. Two tablets per intake. The tablet should be held in the mouth until complete dissolution. 2 tablets 3 times a day without food (i.e. 15-30 min prior to meal or 15-30 min after meal). Rengalin: Oral administration.	Placebo n=116 participants at risk Oral administration. Two tablets per intake. The tablet should be held in the mouth until complete dissolution. 2 tablets 3 times a day without food (i.e. 15-30 min prior to meal or 15-30 min after meal). Placebo: Oral administration.
Gastrointestinal disorders Angular cheilitis	0.00% 0/121 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).	0.86% 1/116 • Number of events 1 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).
Gastrointestinal disorders Nausea	2.5% 3/121 • Number of events 3 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).	0.86% 1/116 • Number of events 1 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).
Gastrointestinal disorders Dry mouth	0.83% 1/121 • Number of events 1 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).	0.00% 0/116 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).
Infections and infestations Labial herpes	0.00% 0/121 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).	0.86% 1/116 • Number of events 1 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).
Vascular disorders The rise in blood pressure	0.83% 1/121 • Number of events 1 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).	0.00% 0/116 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).
Respiratory, thoracic and mediastinal disorders Difficulty passing sputum	0.83% 1/121 • Number of events 1 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).	0.00% 0/116 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).
Respiratory, thoracic and mediastinal disorders Rhinorrhea	0.83% 1/121 • Number of events 1 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).	0.00% 0/116 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).
Skin and subcutaneous tissue disorders Itchy palms	0.00% 0/121 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).	0.86% 1/116 • Number of events 1 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).
Musculoskeletal and connective tissue disorders Lumbar pain	0.00% 0/121 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).	0.86% 1/116 • Number of events 1 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).
Musculoskeletal and connective tissue disorders Pain in the subscapularis	0.00% 0/121 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).	0.86% 1/116 • Number of events 1 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).
Nervous system disorders Headache	2.5% 3/121 • Number of events 3 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).	1.7% 2/116 • Number of events 2 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).
Nervous system disorders Sleep disturbance	0.00% 0/121 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).	0.86% 1/116 • Number of events 1 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).
Nervous system disorders Dizziness	0.83% 1/121 • Number of events 1 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).	0.00% 0/116 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).
Eye disorders Visual impairment	0.83% 1/121 • Number of events 1 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).	0.00% 0/116 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).
Ear and labyrinth disorders Tinnitus	0.83% 1/121 • Number of events 1 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).	0.00% 0/116 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).
Vascular disorders Worsening hypertension	0.00% 0/121 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).	0.86% 1/116 • Number of events 1 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).
Vascular disorders Hypertensive crisis	0.83% 1/121 • Number of events 1 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).	0.00% 0/116 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).
General disorders General weakness	0.00% 0/121 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).	0.86% 1/116 • Number of events 1 • 4 weeks (screening + randomization - up to 1 days, study therapy - 4 weeks).