Trial Outcomes & Findings for Clinical Trial of Efficacy and Safety of Divaza for Adjustment of Oxidative Disorders in Patients With Cerebral Atherosclerosis (NCT NCT03485495)
NCT ID: NCT03485495
Last Updated: 2021-08-26
Results Overview
Based on laboratory evaluation. Change in the mean resistance of lipoprotein (LP) to lipid peroxidation (LPO) after 12-week therapy versus baseline.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
124 participants
Primary outcome timeframe
12 weeks of the observation period.
Results posted on
2021-08-26
Participant Flow
Participant milestones
| Measure |
Divaza
Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Divaza: Oral administration.
|
Placebo
Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Placebo: Oral administration.
|
|---|---|---|
|
Overall Study
STARTED
|
65
|
59
|
|
Overall Study
COMPLETED
|
64
|
59
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Divaza
Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Divaza: Oral administration.
|
Placebo
Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Placebo: Oral administration.
|
|---|---|---|
|
Overall Study
Non-compliance with inclusion criteria
|
1
|
0
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Divaza
n=65 Participants
Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Divaza: Oral administration.
|
Placebo
n=59 Participants
Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Placebo: Oral administration.
|
Total
n=124 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
61.4 years
STANDARD_DEVIATION 7.8 • n=65 Participants
|
59.8 years
STANDARD_DEVIATION 7.4 • n=59 Participants
|
60.7 years
STANDARD_DEVIATION 7.6 • n=124 Participants
|
|
Sex: Female, Male
Female
|
51 Participants
n=65 Participants
|
40 Participants
n=59 Participants
|
91 Participants
n=124 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=65 Participants
|
19 Participants
n=59 Participants
|
33 Participants
n=124 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Russia
|
65 participants
n=65 Participants
|
59 participants
n=59 Participants
|
124 participants
n=124 Participants
|
PRIMARY outcome
Timeframe: 12 weeks of the observation period.Population: 1 patient in Divaza group had no laboratory data.
Based on laboratory evaluation. Change in the mean resistance of lipoprotein (LP) to lipid peroxidation (LPO) after 12-week therapy versus baseline.
Outcome measures
| Measure |
Divaza
n=63 Participants
Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Divaza: Oral administration.
|
Placebo
n=59 Participants
Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Placebo: Oral administration.
|
|---|---|---|
|
Change in Mean Value of Lipoprotein Resistance to LPO.
Resistance of LP to LPO at baseline
|
42.4 seconds
Standard Deviation 13.1
|
42.9 seconds
Standard Deviation 11.2
|
|
Change in Mean Value of Lipoprotein Resistance to LPO.
Resistance of LP to LPO after 12 weeks
|
55.6 seconds
Standard Deviation 12.5
|
49.4 seconds
Standard Deviation 14.3
|
|
Change in Mean Value of Lipoprotein Resistance to LPO.
∆ between baseline and after 12 weeks
|
14.8 seconds
Standard Deviation 14.7
|
6.4 seconds
Standard Deviation 16.9
|
SECONDARY outcome
Timeframe: 12 weeks of the observation period.Population: 8 patients in Divaza group and 2 patients in Placebo group had no data for week 12.
MoCA (Montreal Cognitive Assessment) score +1 and over after 12-week therapy versus baseline. Minimum score is 0, maximum score is 30. Higher values represent a better outcome.
Outcome measures
| Measure |
Divaza
n=56 Participants
Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Divaza: Oral administration.
|
Placebo
n=57 Participants
Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Placebo: Oral administration.
|
|---|---|---|
|
Percentage of Patients With Improved Cognitive Function.
|
56 Participants
|
51 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 weeks of the observation periodPopulation: 1 patient in Divaza group had no laboratory data.
Based on laboratory evaluation. Change in mean level of preformed LP products, predominantly lipid hydroperoxides after 12-week therapy versus baseline. The following kinetic parameters of chemiluminescence were measured: rapid chemiluminescence flare amplitude reflecting the stationary level of lipid hydroperoxides.
Outcome measures
| Measure |
Divaza
n=63 Participants
Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Divaza: Oral administration.
|
Placebo
n=59 Participants
Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Placebo: Oral administration.
|
|---|---|---|
|
Change in Mean Level of Preformed LP Products (Mainly Lipid Hydroperoxides).
Level of preformed LPO products at baseline
|
72.5 Mcmol / L
Standard Deviation 14.1
|
72.8 Mcmol / L
Standard Deviation 12.9
|
|
Change in Mean Level of Preformed LP Products (Mainly Lipid Hydroperoxides).
Level of preformed LPO products after 12 weeks
|
67.7 Mcmol / L
Standard Deviation 13.1
|
69.9 Mcmol / L
Standard Deviation 11.7
|
|
Change in Mean Level of Preformed LP Products (Mainly Lipid Hydroperoxides).
∆ between baseline and after 12 weeks
|
-3.2 Mcmol / L
Standard Deviation 9.6
|
-2.9 Mcmol / L
Standard Deviation 8.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 weeks of the observation period.Population: 1 patient in Divaza group had no laboratory data.
Based on laboratory evaluation. Change in mean value of lipoprotein ability for oxidation after 12-week therapy versus baseline. For plasma, draw blood into an EDTA tube and gently invert the tube 8 to 10 times to mix the anticoagulant. Centrifuge the tube, remove the stopper and draw off approximately 2/3 of the upper plasma layer into a labeled transfer tube using a transfer pipet bulb. Plasma must be separated from cells within 45 minutes of venipuncture. Measurement of oxidized LDL (oxLDL) has been incorporated into clinical practice in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases, especially as it pertains to the evaluation of oxidative stress. Oxidized LDL-particles are considered to be an important driving factor in the pathophysiology of atherosclerosis and oxLDL measurement has been used to test the efficacy of CVD drugs (eg, statins) to reduce oxidative stress.
Outcome measures
| Measure |
Divaza
n=63 Participants
Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Divaza: Oral administration.
|
Placebo
n=59 Participants
Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Placebo: Oral administration.
|
|---|---|---|
|
Change in Mean Value of Lipoprotein Ability for Oxidation.
LP ability for oxidation after 12 weeks
|
1024.1 mV
Standard Deviation 226.7
|
1040.6 mV
Standard Deviation 217.7
|
|
Change in Mean Value of Lipoprotein Ability for Oxidation.
∆ between baseline and after 12 weeks
|
-12.1 mV
Standard Deviation 192.1
|
57.0 mV
Standard Deviation 241.5
|
|
Change in Mean Value of Lipoprotein Ability for Oxidation.
LP ability for oxidation at baseline
|
1027.3 mV
Standard Deviation 204.7
|
993.8 mV
Standard Deviation 264.1
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 weeks of the observation period.Based on laboratory evaluation. Change in the mean concentration of nitrites and nitrates in serum after 12-week therapy versus baseline. Griess Reaction assay. In the Griess reaction, first reported by Johann Peter Griess in 1879 as a method of analysis of nitrite (NO2-), nitrite reacts under acidic conditions with sulfanilic acid (HO3SC6H4NH2) to form a diazonium cation (HO3SC6H4-Ntriple bondN+) which subsequently couples to the aromatic amine 1-naphthylamine (C10H7NH2) to produce a red-violet coloured (λmax ≈ 540 nm), water-soluble azo dye (HO3SC6H4-Ndouble bondN-C10H6NH2).
Outcome measures
| Measure |
Divaza
n=7 Participants
Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Divaza: Oral administration.
|
Placebo
n=8 Participants
Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Placebo: Oral administration.
|
|---|---|---|
|
Change in Mean Value of NO Products Serum Concentration.
NO-2 level after 12 weeks
|
43.9 μmol per liter
Standard Deviation 22.2
|
52.5 μmol per liter
Standard Deviation 35.9
|
|
Change in Mean Value of NO Products Serum Concentration.
NO-2 level (after cuff test) after 12 weeks
|
57.0 μmol per liter
Standard Deviation 14.5
|
51.0 μmol per liter
Standard Deviation 25.9
|
|
Change in Mean Value of NO Products Serum Concentration.
NO-3 level at baseline
|
41.3 μmol per liter
Standard Deviation 14.9
|
69.0 μmol per liter
Standard Deviation 28.9
|
|
Change in Mean Value of NO Products Serum Concentration.
NO-3 level (after cuff test) at baseline
|
38.4 μmol per liter
Standard Deviation 16.5
|
79.1 μmol per liter
Standard Deviation 33.5
|
|
Change in Mean Value of NO Products Serum Concentration.
NO-3 level after 12 weeks
|
51.7 μmol per liter
Standard Deviation 23.9
|
63.3 μmol per liter
Standard Deviation 36.8
|
|
Change in Mean Value of NO Products Serum Concentration.
NO-3 level (after cuff test) after 12 weeks
|
64.0 μmol per liter
Standard Deviation 15.6
|
61.1 μmol per liter
Standard Deviation 27.9
|
|
Change in Mean Value of NO Products Serum Concentration.
NO-2 level at baseline
|
35.9 μmol per liter
Standard Deviation 16.0
|
62.8 μmol per liter
Standard Deviation 28.0
|
|
Change in Mean Value of NO Products Serum Concentration.
NO-2 level (after cuff test) at baseline
|
31.8 μmol per liter
Standard Deviation 16.1
|
69.6 μmol per liter
Standard Deviation 32.3
|
|
Change in Mean Value of NO Products Serum Concentration.
NO level at baseline
|
5.4 μmol per liter
Standard Deviation 2.3
|
6.3 μmol per liter
Standard Deviation 4.1
|
|
Change in Mean Value of NO Products Serum Concentration.
NO level (after cuff test) at baseline
|
6.6 μmol per liter
Standard Deviation 1.8
|
9.5 μmol per liter
Standard Deviation 4.0
|
|
Change in Mean Value of NO Products Serum Concentration.
NO level after 12
|
7.8 μmol per liter
Standard Deviation 3.9
|
10.7 μmol per liter
Standard Deviation 4.5
|
|
Change in Mean Value of NO Products Serum Concentration.
NO level (after cuff test) after 12 weeks
|
7.0 μmol per liter
Standard Deviation 2.8
|
10.1 μmol per liter
Standard Deviation 5.2
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 weeks of the observation period.Population: ADP-AP - platelet aggregation (PA) induced by adenosine diphosphate (ADP) ADR-AP - platelet aggregation (PA) induced by adrenaline (ADR)
Based on laboratory evaluation. Change in mean platelet aggregation after 12-week therapy versus baseline.
Outcome measures
| Measure |
Divaza
n=7 Participants
Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Divaza: Oral administration.
|
Placebo
n=8 Participants
Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Placebo: Oral administration.
|
|---|---|---|
|
Change in Mean Value of Platelet Aggregation.
ADP-PA at baseline
|
46.9 percentage aggregation
Standard Deviation 13.8
|
44.6 percentage aggregation
Standard Deviation 14.1
|
|
Change in Mean Value of Platelet Aggregation.
ADP-PA (after cuff test) at baseline
|
45.0 percentage aggregation
Standard Deviation 14.0
|
51.9 percentage aggregation
Standard Deviation 15.7
|
|
Change in Mean Value of Platelet Aggregation.
ADP-PA after 12 weeks
|
45.3 percentage aggregation
Standard Deviation 12.5
|
46.3 percentage aggregation
Standard Deviation 9.4
|
|
Change in Mean Value of Platelet Aggregation.
ADP-PA (after cuff test) after 12 weeks
|
49.7 percentage aggregation
Standard Deviation 14.6
|
52.5 percentage aggregation
Standard Deviation 11.6
|
|
Change in Mean Value of Platelet Aggregation.
ADR-PA at baseline
|
48.4 percentage aggregation
Standard Deviation 12.2
|
47.8 percentage aggregation
Standard Deviation 16.4
|
|
Change in Mean Value of Platelet Aggregation.
ADR-PA (after cuff test) at baseline
|
44.7 percentage aggregation
Standard Deviation 13.3
|
53.1 percentage aggregation
Standard Deviation 16.8
|
|
Change in Mean Value of Platelet Aggregation.
ADR-PA after 12 weeks
|
47.7 percentage aggregation
Standard Deviation 11.8
|
51.4 percentage aggregation
Standard Deviation 11.3
|
|
Change in Mean Value of Platelet Aggregation.
ADR-PA (after cuff test) after 12 weeks
|
54.1 percentage aggregation
Standard Deviation 8.6
|
57.4 percentage aggregation
Standard Deviation 14.6
|
Adverse Events
Divaza
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Divaza
n=64 participants at risk
Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Divaza: Oral administration.
|
Placebo
n=59 participants at risk
Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Placebo: Oral administration.
|
|---|---|---|
|
Gastrointestinal disorders
Odinophagy
|
1.6%
1/64 • Number of events 1 • During the treatment period - 12 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
|
0.00%
0/59 • During the treatment period - 12 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
|
|
Infections and infestations
Nasopharyngitis
|
1.6%
1/64 • Number of events 1 • During the treatment period - 12 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
|
0.00%
0/59 • During the treatment period - 12 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
|
|
Infections and infestations
Respiratory tract infection
|
1.6%
1/64 • Number of events 1 • During the treatment period - 12 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
|
1.7%
1/59 • Number of events 1 • During the treatment period - 12 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
|
|
Investigations
Increased blood pressure
|
0.00%
0/64 • During the treatment period - 12 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
|
1.7%
1/59 • Number of events 1 • During the treatment period - 12 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
|
|
Respiratory, thoracic and mediastinal disorders
Nosebleed
|
0.00%
0/64 • During the treatment period - 12 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
|
1.7%
1/59 • Number of events 1 • During the treatment period - 12 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
|
|
Nervous system disorders
Headache
|
1.6%
1/64 • Number of events 1 • During the treatment period - 12 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
|
0.00%
0/59 • During the treatment period - 12 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
1.6%
1/64 • Number of events 1 • During the treatment period - 12 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
|
0.00%
0/59 • During the treatment period - 12 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).
|
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