Trial Outcomes & Findings for Safety Study of RMJH-111b to Treat Essential Hypertension (NCT NCT02822222)
NCT ID: NCT02822222
Last Updated: 2020-09-23
Results Overview
Safety \& tolerability were primarily assessed based on the incidence of reported TEAEs by system organ class \& preferred term, as well as by categories: TEAE, severe TEAE, serious TEAE, drug-related TEAE, drug-related severe TEAE, drug-related serious TEAE, TEAE leading to discontinuation, \& TEAE with outcome of death. Drug-related TEAEs were defined as TEAEs assigned a Study Drug (active or placebo) relationship of "adverse reaction" or "suspected adverse reaction". TEAEs were coded using the Medical Dictionary for Regulatory Activities, version 19.0. The severity of TEAEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. TEAEs were defined as any adverse event that started or increased in severity after the first randomized dose of Study Drug on Day 4 through the Final Study Visit (8 +/-3 days after last randomized dose).
COMPLETED
PHASE1/PHASE2
22 participants
14 days +/- 3 days
2020-09-23
Participant Flow
This trial was conducted at a single Investigational Site (Orange County Research Center) in Tustin, CA. All subject recruitment procedures and materials were reviewed \& approved by a central IRB prior to their use. The 1st screening visit was May 31, 2016, the 1st subject was enrolled on June 10, 2016, \& the last subject visit was July 7, 2016.
Randomization to treatment took place on Day 4, following the 7-day washout period \& the 3-day run-in placebo period. Only subjects that continued to meet eligibility criteria following the Day 4 baseline procedures were randomized.
Participant milestones
| Measure |
RMJH-111b
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Overall Study
STARTED
|
16
|
6
|
|
Overall Study
COMPLETED
|
15
|
6
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
RMJH-111b
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Overall Study
Protocol requirement SBP<110 mmHg
|
1
|
0
|
Baseline Characteristics
Safety Study of RMJH-111b to Treat Essential Hypertension
Baseline characteristics by cohort
| Measure |
RMJH-111b
n=16 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
Total
n=22 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
15 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
9 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
14 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Age, Continuous
|
58.08 years
STANDARD_DEVIATION 8.882 • n=5 Participants
|
61.36 years
STANDARD_DEVIATION 5.889 • n=7 Participants
|
58.98 years
STANDARD_DEVIATION 8.175 • n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
16 participants
n=5 Participants
|
6 participants
n=7 Participants
|
22 participants
n=5 Participants
|
|
Height
|
170.3 cm
STANDARD_DEVIATION 8.79 • n=5 Participants
|
174.0 cm
STANDARD_DEVIATION 10.43 • n=7 Participants
|
171.3 cm
STANDARD_DEVIATION 9.16 • n=5 Participants
|
|
Weight
|
90.54 kg
STANDARD_DEVIATION 14.865 • n=5 Participants
|
89.35 kg
STANDARD_DEVIATION 9.492 • n=7 Participants
|
90.21 kg
STANDARD_DEVIATION 13.401 • n=5 Participants
|
|
Heart rate
|
72.50 beats per minute
STANDARD_DEVIATION 7.572 • n=5 Participants
|
66.33 beats per minute
STANDARD_DEVIATION 8.710 • n=7 Participants
|
70.82 beats per minute
STANDARD_DEVIATION 8.180 • n=5 Participants
|
|
Respiration rate
|
12.75 breaths per minute
STANDARD_DEVIATION 1.000 • n=5 Participants
|
12.33 breaths per minute
STANDARD_DEVIATION 0.816 • n=7 Participants
|
12.64 breaths per minute
STANDARD_DEVIATION 0.953 • n=5 Participants
|
|
Temperature
|
36.59 degrees Celsius
STANDARD_DEVIATION 0.208 • n=5 Participants
|
36.60 degrees Celsius
STANDARD_DEVIATION 0.063 • n=7 Participants
|
36.60 degrees Celsius
STANDARD_DEVIATION 0.179 • n=5 Participants
|
|
Seated SBP
|
160.4 mmHg
STANDARD_DEVIATION 8.58 • n=5 Participants
|
162.0 mmHg
STANDARD_DEVIATION 5.06 • n=7 Participants
|
160.9 mmHg
STANDARD_DEVIATION 7.69 • n=5 Participants
|
|
Seated DBP
|
101.4 mmHg
STANDARD_DEVIATION 5.18 • n=5 Participants
|
102.0 mmHg
STANDARD_DEVIATION 5.18 • n=7 Participants
|
101.6 mmHg
STANDARD_DEVIATION 5.06 • n=5 Participants
|
|
SBPday
|
149.8 mmHg
STANDARD_DEVIATION 13.27 • n=5 Participants
|
147.4 mmHg
STANDARD_DEVIATION 9.61 • n=7 Participants
|
149.1 mmHg
STANDARD_DEVIATION 12.22 • n=5 Participants
|
|
SBPnight
|
138.0 mmHg
STANDARD_DEVIATION 17.34 • n=5 Participants
|
133.3 mmHg
STANDARD_DEVIATION 9.31 • n=7 Participants
|
136.7 mmHg
STANDARD_DEVIATION 15.48 • n=5 Participants
|
|
SBP24hr
|
145.3 mmHg
STANDARD_DEVIATION 14.02 • n=5 Participants
|
141.2 mmHg
STANDARD_DEVIATION 8.07 • n=7 Participants
|
144.2 mmHg
STANDARD_DEVIATION 12.62 • n=5 Participants
|
|
DBPday
|
92.6 mmHg
STANDARD_DEVIATION 11.20 • n=5 Participants
|
93.3 mmHg
STANDARD_DEVIATION 9.81 • n=7 Participants
|
92.8 mmHg
STANDARD_DEVIATION 10.61 • n=5 Participants
|
|
DBPnight
|
82.3 mmHg
STANDARD_DEVIATION 12.14 • n=5 Participants
|
82.6 mmHg
STANDARD_DEVIATION 3.23 • n=7 Participants
|
82.4 mmHg
STANDARD_DEVIATION 10.38 • n=5 Participants
|
|
DBP24hr
|
88.6 mmHg
STANDARD_DEVIATION 10.91 • n=5 Participants
|
88.8 mmHg
STANDARD_DEVIATION 6.04 • n=7 Participants
|
88.7 mmHg
STANDARD_DEVIATION 9.69 • n=5 Participants
|
|
Total Serum Magnesium AUC
|
41.4 mEq*24hr/L
STANDARD_DEVIATION 2.42 • n=5 Participants
|
42.8 mEq*24hr/L
STANDARD_DEVIATION 2.76 • n=7 Participants
|
41.8 mEq*24hr/L
STANDARD_DEVIATION 2.53 • n=5 Participants
|
|
Total Serum Magnesium Concentration
|
1.75 mEq/L
STANDARD_DEVIATION 0.103 • n=5 Participants
|
1.78 mEq/L
STANDARD_DEVIATION 0.117 • n=7 Participants
|
1.76 mEq/L
STANDARD_DEVIATION 0.105 • n=5 Participants
|
|
24-hour urinary magnesium excretion
|
7.3 mEq/24 hrs
STANDARD_DEVIATION 2.59 • n=5 Participants
|
7.0 mEq/24 hrs
STANDARD_DEVIATION 4.34 • n=7 Participants
|
7.2 mEq/24 hrs
STANDARD_DEVIATION 3.05 • n=5 Participants
|
|
12-lead ECG Ventricular Rate
|
70.31 bpm
STANDARD_DEVIATION 9.904 • n=5 Participants
|
65.83 bpm
STANDARD_DEVIATION 14.851 • n=7 Participants
|
69.09 bpm
STANDARD_DEVIATION 11.258 • n=5 Participants
|
|
12-Lead ECG Intervals
RR Interval
|
863.31 msec
STANDARD_DEVIATION 113.781 • n=5 Participants
|
944.17 msec
STANDARD_DEVIATION 199.272 • n=7 Participants
|
885.36 msec
STANDARD_DEVIATION 141.635 • n=5 Participants
|
|
12-Lead ECG Intervals
PR Interval
|
168.38 msec
STANDARD_DEVIATION 18.143 • n=5 Participants
|
155.67 msec
STANDARD_DEVIATION 10.985 • n=7 Participants
|
164.91 msec
STANDARD_DEVIATION 17.246 • n=5 Participants
|
|
12-Lead ECG Intervals
QRS Interval
|
90.00 msec
STANDARD_DEVIATION 9.033 • n=5 Participants
|
97.67 msec
STANDARD_DEVIATION 19.159 • n=7 Participants
|
92.09 msec
STANDARD_DEVIATION 12.566 • n=5 Participants
|
|
12-Lead ECG Intervals
QT Interval
|
398.56 msec
STANDARD_DEVIATION 24.916 • n=5 Participants
|
416.00 msec
STANDARD_DEVIATION 48.233 • n=7 Participants
|
403.32 msec
STANDARD_DEVIATION 32.566 • n=5 Participants
|
|
12-Lead ECG Intervals
Corrected QT Interval
|
416.25 msec
STANDARD_DEVIATION 21.592 • n=5 Participants
|
424.00 msec
STANDARD_DEVIATION 23.639 • n=7 Participants
|
418.36 msec
STANDARD_DEVIATION 21.875 • n=5 Participants
|
|
12-Lead ECG Diagnosis
Normal
|
9 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
12-Lead ECG Diagnosis
Abnormal NCS
|
7 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
12-Lead ECG Diagnosis
Abnormal CS
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Patellar Reflex Score
2+
|
11 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Patellar Reflex Score
1+
|
5 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 14 days +/- 3 daysPopulation: Safety population = all randomized subjects who received at least one dose of Study Drug (active or placebo).
Safety \& tolerability were primarily assessed based on the incidence of reported TEAEs by system organ class \& preferred term, as well as by categories: TEAE, severe TEAE, serious TEAE, drug-related TEAE, drug-related severe TEAE, drug-related serious TEAE, TEAE leading to discontinuation, \& TEAE with outcome of death. Drug-related TEAEs were defined as TEAEs assigned a Study Drug (active or placebo) relationship of "adverse reaction" or "suspected adverse reaction". TEAEs were coded using the Medical Dictionary for Regulatory Activities, version 19.0. The severity of TEAEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. TEAEs were defined as any adverse event that started or increased in severity after the first randomized dose of Study Drug on Day 4 through the Final Study Visit (8 +/-3 days after last randomized dose).
Outcome measures
| Measure |
RMJH-111b
n=16 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Treatment Emergent Adverse Events (TEAEs)
TEAE
|
5 Participants
|
1 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Treatment Emergent Adverse Events (TEAEs)
Severe TEAE
|
0 Participants
|
0 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Treatment Emergent Adverse Events (TEAEs)
Serious TEAE
|
0 Participants
|
0 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Treatment Emergent Adverse Events (TEAEs)
Drug-related TEAE
|
2 Participants
|
0 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Treatment Emergent Adverse Events (TEAEs)
Drug-related severe TEAE
|
0 Participants
|
0 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Treatment Emergent Adverse Events (TEAEs)
Drug-related serious TEAE
|
0 Participants
|
0 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Treatment Emergent Adverse Events (TEAEs)
TEAE leading to discontinuation from study
|
0 Participants
|
0 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Treatment Emergent Adverse Events (TEAEs)
TEAE with outcome of death
|
0 Participants
|
0 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Treatment Emergent Adverse Events (TEAEs)
Mild abdominal pain upper
|
1 Participants
|
0 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Treatment Emergent Adverse Events (TEAEs)
Moderate constipation
|
1 Participants
|
0 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Treatment Emergent Adverse Events (TEAEs)
Mild diarrhoea
|
2 Participants
|
0 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Treatment Emergent Adverse Events (TEAEs)
Mild flatulence
|
1 Participants
|
0 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Treatment Emergent Adverse Events (TEAEs)
Mild headache
|
1 Participants
|
1 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Treatment Emergent Adverse Events (TEAEs)
Mild cough
|
2 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: 8 daysPopulation: Safety population = all randomized subjects who received at least 1 dose of Study Drug. 1 subject in RMJH-111b arm was discontinued on Day 9 due to protocol-specified criterion \[SBP\<110 mmHg; the SBPs (102-109 mmHg) were not associated with clinical symptoms \& were not assigned as TEAEs\] \& is therefore missing Day 10-11 assessment (i.e., n=15).
Change in the mean value of 24-hour urinary magnesium excretion from baseline (Day 3 to pre-dose Day 4) to end of treatment (Day 10 to Day 11). Mean values that are negative represent a decrease in that value from baseline, whereas values that are positive represent an increase.
Outcome measures
| Measure |
RMJH-111b
n=15 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 24-hour Urinary Magnesium Excretion
|
9.1 mEq/24 hours
Standard Deviation 5.44
|
-1.3 mEq/24 hours
Standard Deviation 5.57
|
PRIMARY outcome
Timeframe: 7 daysPopulation: Safety population = all randomized subjects who received at least 1 dose of Study Drug. 1 subject in RMJH-111b arm was discontinued on Day 9 due to protocol-specified criterion \[SBP\<110 mmHg; the SBPs (102-109 mmHg) were not associated with clinical symptoms \& were not assigned as TEAEs\] \& is therefore missing Day 11 assessments (i.e., n=15).
Changes in the mean values for seated SBP \& DBP from baseline (pre-dose Day 4) to end of treatment (Day 11). Mean values that are negative represent a decrease in that value from baseline, whereas values that are positive represent an increase.
Outcome measures
| Measure |
RMJH-111b
n=15 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in Seated SBP and DBP
Change in seated SBP
|
-14.6 mmHg
Standard Deviation 13.58
|
-7.2 mmHg
Standard Deviation 7.36
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in Seated SBP and DBP
Change in seated DBP
|
-6.4 mmHg
Standard Deviation 6.08
|
-2.3 mmHg
Standard Deviation 6.25
|
PRIMARY outcome
Timeframe: 10 daysPopulation: Safety population = all randomized subjects who received at least 1 dose of Study Drug. 1 subject in RMJH-111b arm was discontinued on Day 9 due to protocol-specified criterion \[SBP\<110 mmHg; the SBPs (102-109 mmHg) were not associated with clinical symptoms \& were not assigned as TEAEs\] \& is therefore missing Day 11 assessment (i.e., n=15).
Change in mean body weight from baseline (Day 1) to end of treatment (Day 11). The weight measurements were made using a calibrated scale with the subject wearing light clothes and no shoes. Mean values that are negative represent a decrease in that value from baseline, whereas values that are positive represent an increase.
Outcome measures
| Measure |
RMJH-111b
n=15 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in Body Weight
|
-1.09 kg
Standard Deviation 2.372
|
-0.79 kg
Standard Deviation 1.421
|
PRIMARY outcome
Timeframe: Up to 6 daysPopulation: Safety population = all randomized subjects who received at least 1 dose of Study Drug
Change in mean 12-lead ECG ventricular rate from baseline (Screening or Day 1) to 3 hours after the first randomized dose (Day 4). Mean values that are negative represent a decrease in that value from baseline, whereas values that are positive represent an increase. The ECG assessments were recorded after the subject was resting at least 5 minutes in the supine position in a quiet environment.
Outcome measures
| Measure |
RMJH-111b
n=16 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Ventricular Rate (3 Hours After 1st Dose)
|
-0.31 bpm
Standard Deviation 8.554
|
-5.17 bpm
Standard Deviation 6.735
|
PRIMARY outcome
Timeframe: Up to 13 daysPopulation: Safety population = all randomized subjects who received at least 1 dose of Study Drug. 1 subject in RMJH-111b arm was discontinued on Day 9 due to protocol-specified criterion \[SBP\<110 mmHg; the SBPs (102-109 mmHg) were not associated with clinical symptoms \& were not assigned as TEAEs\] \& is therefore missing Day 11 assessment (i.e., n=15).
Change in mean 12-lead ECG ventricular rate from baseline (Screening or Day 1) to after the last randomized dose (Day 11). Mean values that are negative represent a decrease in that value from baseline, whereas values that are positive represent an increase. The ECG assessments were recorded after the subject was resting at least 5 minutes in the supine position in a quiet environment.
Outcome measures
| Measure |
RMJH-111b
n=15 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Ventricular Rate (After Last Dose)
|
4.73 bpm
Standard Deviation 10.579
|
-3.83 bpm
Standard Deviation 8.519
|
PRIMARY outcome
Timeframe: Up to 6 daysPopulation: Safety population = all randomized subjects who received at least 1 dose of Study Drug
Change in mean 12-lead ECG intervals (RR interval, PR interval, QRS interval, QT interval, corrected QT interval based on Fridericia formula) from baseline (Screening or Day 1) to 3 hours after the first randomized dose (Day 4). Mean values that are negative represent a decrease in that value from baseline, whereas values that are positive represent an increase. The ECG assessments were recorded after the subject was resting at least 5 minutes in the supine position in a quiet environment.
Outcome measures
| Measure |
RMJH-111b
n=16 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Intervals (3 Hours After 1st Dose)
Change in RR Interval
|
8.06 msec
Standard Deviation 102.179
|
55.33 msec
Standard Deviation 96.804
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Intervals (3 Hours After 1st Dose)
Change in PR Interval
|
0.75 msec
Standard Deviation 13.364
|
8.67 msec
Standard Deviation 4.502
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Intervals (3 Hours After 1st Dose)
Change in QRS Interval
|
-2.63 msec
Standard Deviation 4.113
|
2.33 msec
Standard Deviation 4.274
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Intervals (3 Hours After 1st Dose)
Change in QT Interval
|
-5.06 msec
Standard Deviation 26.727
|
-0.33 msec
Standard Deviation 23.372
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Intervals (3 Hours After 1st Dose)
Change in Corrected QT Interval
|
-5.06 msec
Standard Deviation 16.097
|
-9.17 msec
Standard Deviation 16.005
|
PRIMARY outcome
Timeframe: Up to 13 daysPopulation: Safety population = all randomized subjects who received at least 1 dose of Study Drug. 1 subject in RMJH-111b arm was discontinued on Day 9 due to protocol-specified criterion \[SBP\<110 mmHg; the SBPs (102-109 mmHg) were not associated with clinical symptoms \& were not assigned as TEAEs\] \& is therefore missing Day 11 assessment (i.e., n=15).
Change in mean 12-lead ECG intervals (RR interval, PR interval, QRS interval, QT interval, corrected QT interval based on Fridericia formula) from baseline (Screening or Day 1) to after the last randomized dose (Day 11). Mean values that are negative represent a decrease in that value from baseline, whereas values that are positive represent an increase. The ECG assessments were recorded after the subject was resting at least 5 minutes in the supine position in a quiet environment.
Outcome measures
| Measure |
RMJH-111b
n=15 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Intervals (After Last Dose)
Change in RR Interval
|
-57.00 msec
Standard Deviation 122.412
|
29.67 msec
Standard Deviation 82.921
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Intervals (After Last Dose)
Change in PR Interval
|
-4.00 msec
Standard Deviation 12.806
|
8.33 msec
Standard Deviation 13.530
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Intervals (After Last Dose)
Change in QRS Interval
|
-1.33 msec
Standard Deviation 3.677
|
-0.67 msec
Standard Deviation 5.317
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Intervals (After Last Dose)
Change in QT Interval
|
-11.67 msec
Standard Deviation 24.732
|
5.67 msec
Standard Deviation 22.393
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Intervals (After Last Dose)
Change in Corrected QT Interval
|
-1.47 msec
Standard Deviation 11.332
|
-0.33 msec
Standard Deviation 12.307
|
PRIMARY outcome
Timeframe: Up to 6 daysPopulation: Safety population = all randomized subjects who received at least 1 dose of Study Drug
Change in 12-lead ECG diagnosis \[i.e., normal to abnormal not clinically significant (NCS); normal to abnormal clinically significant (CS); abnormal NCS to abnormal CS; remained abnormal NCS; remained normal\] from baseline (Screening or Day 1) to 3 hours after the first randomized dose (Day 4). The ECG was recorded after the subject was resting at least 5 minutes in the supine position in a quiet environment.
Outcome measures
| Measure |
RMJH-111b
n=16 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Diagnosis (3 Hours After 1st Dose)
Changed from Normal to Abnormal NCS
|
1 Participants
|
1 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Diagnosis (3 Hours After 1st Dose)
Changed from Normal to Abnormal CS
|
0 Participants
|
0 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Diagnosis (3 Hours After 1st Dose)
Changed from Abnormal NCS to Abnormal CS
|
0 Participants
|
0 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Diagnosis (3 Hours After 1st Dose)
Remained Abnormal NCS
|
7 Participants
|
3 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Diagnosis (3 Hours After 1st Dose)
Remained Normal
|
8 Participants
|
2 Participants
|
PRIMARY outcome
Timeframe: Up to 13 daysPopulation: Safety population = all randomized subjects who received at least 1 dose of Study Drug. 1 subject in RMJH-111b arm was discontinued on Day 9 due to protocol-specified criterion \[SBP\<110 mmHg; the SBPs (102-109 mmHg) were not associated with clinical symptoms \& were not assigned as TEAEs\] \& is therefore missing Day 11 assessment (i.e., n=15).
Change in 12-lead ECG diagnosis \[i.e., normal to abnormal not clinically significant (NCS); normal to abnormal clinically significant (CS); abnormal NCS to abnormal CS; remained abnormal NCS; remained normal\] from baseline (Screening or Day 1) to after the last randomized dose (Day 11). The ECG was recorded after the subject was resting at least 5 minutes in the supine position in a quiet environment.
Outcome measures
| Measure |
RMJH-111b
n=15 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Diagnosis (After Last Dose)
Changed from Normal to Abnormal NCS
|
1 Participants
|
0 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Diagnosis (After Last Dose)
Changed from Normal to Abnormal CS
|
0 Participants
|
0 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Diagnosis (After Last Dose)
Changed from Abnormal NCS to Abnormal CS
|
0 Participants
|
0 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Diagnosis (After Last Dose)
Remained Abnormal NCS
|
6 Participants
|
2 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Diagnosis (After Last Dose)
Remained Normal
|
7 Participants
|
3 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in 12-lead ECG Diagnosis (After Last Dose)
Changed from Abnormal NCS to Normal
|
1 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: 14 days +/- 3 daysPopulation: Safety population = all randomized subjects who received at least 1 dose of Study Drug. 1 RMJH-111b subject was discontinued on Day 9 due to protocol requirement \[SBP\<110 mmHg; SBPs (102-109 mmHg) not associated with clinical symptoms \& not assigned as TEAEs\] \& lacked Day 10-11 assessments (i.e., n=15). Subject was at 2+ for Day 4-9 \& Final Visit.
Changes in patellar reflex score from baseline (pre-dose Day 4) to interim time points during the randomized treatment period (prior to each morning dose on Days 5 through 10) and to post-dose time points (Day 11 \& Day 18 ± 3 days). The scoring values included 0, 1+, 2+, 3+, and 4+, where 2+ means normal patellar reflex and lower scores indicate a worsened outcome (1+ means reflex present only with reinforcement and 0 means loss of reflex). The patellar reflex assessment was made with the subject in the seated position, with legs hanging freely from the exam table. Loss of patellar reflex is an early sign of magnesium toxicity, and thus the test serves as an assessment for functional magnesium status. A clinical indication of a safe magnesium dosage regimen included the presence of the patellar reflex (knee jerk).
Outcome measures
| Measure |
RMJH-111b
n=15 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in Patellar Reflex Score
Remained at 2+
|
9 Participants
|
6 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in Patellar Reflex Score
Remained at 1+
|
2 Participants
|
0 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in Patellar Reflex Score
Remained at 2+ except Day 9 (1+)
|
1 Participants
|
0 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in Patellar Reflex Score
Remained at 1+ except Day 5 & 8 (2+)
|
1 Participants
|
0 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in Patellar Reflex Score
Remained at 1+ except Day 18 (2+)
|
1 Participants
|
0 Participants
|
|
Safety and Tolerability of RMJH-111b Compared to Placebo Based on Change in Patellar Reflex Score
Remained 1+ except Days 6, 10, & 11 (2+)
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 8 daysPopulation: PK population = all randomized subjects who received at least 1 dose of Study Drug with valid data for at least 1 pre- \& post-dose assessment. 1 subject in RMJH-111b arm was missing PK assessments beyond Day 8, \& thus is only included in the analyses for Days 3 \& 4 and not for Day 10 (i.e., n = 16 for Days 3 \& 4, but n = 15 for Day 10).
Venous blood samples were collected within 1 hour prior to \& 0.5, 1, 2, 3, 6, \& 12 hours following the morning dose of Study Drug on Days 3 (run-in placebo) and 4, \& within 1 hour prior to \& 0.5, 1, 2, 3, 6, 12, \& 24 hours following the morning dose of Study Drug on Day 10. Blood samples were processed to serum \& assayed for total serum magnesium by a central laboratory. The LLOQ was 0.06 mEq/L. Individual PK parameters for Days 4 \& 10 were to be calculated using corrected concentration-time curves (with individual's baseline assessments of endogenous total serum magnesium at Day 3 subtracted); however, due to small numerical values after correction, the planned PK parameters could not be derived. The analyses were reattempted using the observed values (that include the endogenous levels of magnesium), which allowed AUC0-24 to be derived.
Outcome measures
| Measure |
RMJH-111b
n=16 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Pharmacokinetics of Total Serum Magnesium After Single and Repeated Oral Administrations of RMJH-111b Compared to Placebo Based on AUC
Day 3 (pre-dose)
|
41.4 mEq*24hr/L
Standard Deviation 2.42
|
42.8 mEq*24hr/L
Standard Deviation 2.76
|
|
Pharmacokinetics of Total Serum Magnesium After Single and Repeated Oral Administrations of RMJH-111b Compared to Placebo Based on AUC
Day 4 (1st day of dosing)
|
43.9 mEq*24hr/L
Standard Deviation 2.53
|
42.4 mEq*24hr/L
Standard Deviation 3.03
|
|
Pharmacokinetics of Total Serum Magnesium After Single and Repeated Oral Administrations of RMJH-111b Compared to Placebo Based on AUC
Day 10 (7th day of dosing)
|
43.9 mEq*24hr/L
Standard Deviation 1.87
|
41.7 mEq*24hr/L
Standard Deviation 2.52
|
SECONDARY outcome
Timeframe: 6 daysPopulation: PK population = all randomized subjects who received at least 1 dose of Study Drug with valid data for at least 1 pre- \& post-dose assessment. 1 subject in RMJH-111b arm was missing PK assessments beyond Day 8, \& thus is only included in the analyses for Days 5-8 and not for Days 9-10 (i.e., n = 16 for Days 5-8, but n = 15 for Days 9-10).
Venous blood samples were collected within 1 hour prior to the morning dose of Study Drug (active or placebo) on Days 4, 5, 6, 7, 8, 9, and 10. Blood samples were processed to serum \& assayed for total serum magnesium by a central laboratory (LLOQ = 0.06 mEq/L). Ratios of the individual total serum magnesium trough concentrations at Days 5, 6, 7, 8, 9, and 10 relative to baseline (pre-dose Day 4) were calculated. Observed concentrations (including the endogenous levels of magnesium) were used for this purpose.
Outcome measures
| Measure |
RMJH-111b
n=16 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Pharmacokinetics of Total Serum Magnesium After Single and Repeated Oral Administrations of RMJH-111b Compared to Placebo Based on Trough Concentration Ratio
Day 5/Day 4 trough concentrations
|
1.09 unitless (i.e., ratio of mEq/L to mEq/L)
Standard Deviation 0.059
|
1.00 unitless (i.e., ratio of mEq/L to mEq/L)
Standard Deviation 0.034
|
|
Pharmacokinetics of Total Serum Magnesium After Single and Repeated Oral Administrations of RMJH-111b Compared to Placebo Based on Trough Concentration Ratio
Day 6/Day 4 trough concentrations
|
1.10 unitless (i.e., ratio of mEq/L to mEq/L)
Standard Deviation 0.071
|
0.99 unitless (i.e., ratio of mEq/L to mEq/L)
Standard Deviation 0.041
|
|
Pharmacokinetics of Total Serum Magnesium After Single and Repeated Oral Administrations of RMJH-111b Compared to Placebo Based on Trough Concentration Ratio
Day 7/Day 4 trough concentrations
|
1.08 unitless (i.e., ratio of mEq/L to mEq/L)
Standard Deviation 0.097
|
0.98 unitless (i.e., ratio of mEq/L to mEq/L)
Standard Deviation 0.045
|
|
Pharmacokinetics of Total Serum Magnesium After Single and Repeated Oral Administrations of RMJH-111b Compared to Placebo Based on Trough Concentration Ratio
Day 8/Day 4 trough concentrations
|
1.09 unitless (i.e., ratio of mEq/L to mEq/L)
Standard Deviation 0.087
|
1.01 unitless (i.e., ratio of mEq/L to mEq/L)
Standard Deviation 0.043
|
|
Pharmacokinetics of Total Serum Magnesium After Single and Repeated Oral Administrations of RMJH-111b Compared to Placebo Based on Trough Concentration Ratio
Day 9/Day 4 trough concentrations
|
1.06 unitless (i.e., ratio of mEq/L to mEq/L)
Standard Deviation 0.063
|
1.02 unitless (i.e., ratio of mEq/L to mEq/L)
Standard Deviation 0.058
|
|
Pharmacokinetics of Total Serum Magnesium After Single and Repeated Oral Administrations of RMJH-111b Compared to Placebo Based on Trough Concentration Ratio
Day 10/Day 4 trough concentrations
|
1.02 unitless (i.e., ratio of mEq/L to mEq/L)
Standard Deviation 0.080
|
0.96 unitless (i.e., ratio of mEq/L to mEq/L)
Standard Deviation 0.028
|
SECONDARY outcome
Timeframe: 8 daysPopulation: PK population = all randomized subjects who received at least 1 dose of Study Drug with valid data for at least 1 pre- \& post-dose assessment. 1 subject in RMJH-111b arm was missing PK assessments beyond Day 8, \& thus is only included in the analyses for Days 3 \& 4 and not for Day 10 (i.e., n = 16 for Days 3 and 4, but n = 15 for Day 10).
Urinary excretion of magnesium was assessed over three 24-hour periods. The first urine collection started immediately after the morning dose of run-in placebo on Day 3, and the second and third collections started immediately after the morning dose of Study Drug on Days 4 and 10, respectively. Observed 24-hour urinary magnesium excretion values at Days 3, 4, and 10 (i.e., without subtraction of the Day 3 values to correct for the individual's baseline assessment of endogenous urinary magnesium excretion) were used for comparisons with the total serum magnesium data (as only the observed serum values allowed for PK parameter derivation).
Outcome measures
| Measure |
RMJH-111b
n=16 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Pharmacokinetics of Urine Magnesium After Single and Repeated Oral Administrations of RMJH-111b Compared to Placebo Based on 24-hour Urinary Excretion
Day 3 (pre-dose)
|
7.3 mEq/24 hrs
Standard Deviation 2.59
|
7.0 mEq/24 hrs
Standard Deviation 4.34
|
|
Pharmacokinetics of Urine Magnesium After Single and Repeated Oral Administrations of RMJH-111b Compared to Placebo Based on 24-hour Urinary Excretion
Day 4 (1st day of dosing)
|
9.8 mEq/24 hrs
Standard Deviation 3.90
|
5.7 mEq/24 hrs
Standard Deviation 1.97
|
|
Pharmacokinetics of Urine Magnesium After Single and Repeated Oral Administrations of RMJH-111b Compared to Placebo Based on 24-hour Urinary Excretion
Day 10 (7th day of dosing)
|
16.5 mEq/24 hrs
Standard Deviation 6.23
|
5.7 mEq/24 hrs
Standard Deviation 1.63
|
SECONDARY outcome
Timeframe: 8 daysPopulation: Efficacy population = all randomized subjects who completed 7 days of treatment \& the Day 3-Day 4 and Day 10-Day 11 ABPM assessments. 1 subject in RMJH-111b arm was discontinued on Day 9 due to meeting protocol-specified criterion (SBP \< 110 mmHg). The SBPs (102-109 mmHg) were not associated with clinical symptoms \& were not assigned as TEAEs.
SBPday = mean daytime (8 AM to 4 PM) ABPM SBP. Note, mean values of change that are negative represent a decrease in that value from baseline, whereas values that are positive represent an increase. SBPday was measured twice during the subject's stay at the CRU: baseline measurements were collected from Day 3 to pre-dose Day 4 \& post-dose measurements were collected from Day 10 to Day 11. An Investigational Site staff member placed the cuff on the subject's non-dominant arm \& connected the ABPM at approximately 7 AM (± 60 minutes) on Days 3 \& 10. A pre-dose ABPM reading was recorded immediately prior to the morning dose of run-in period placebo on Day 3 \& the morning dose of treatment period Study Drug (active or placebo) on Day 10. The ABPM was started again immediately after dosing. The ABPM was removed at approximately 8 AM (± 60 minutes) on Days 4 and 11, respectively, but no sooner than 24 hours after the continuous monitoring was initiated.
Outcome measures
| Measure |
RMJH-111b
n=15 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Efficacy of RMJH-111b Compared to Placebo Based on Change From Baseline in SBPday After 7 Days of Treatment
|
-4.6 mmHg
Standard Deviation 11.72
|
1.6 mmHg
Standard Deviation 11.36
|
SECONDARY outcome
Timeframe: 8 daysPopulation: Efficacy population = all randomized subjects who completed 7 days of treatment \& the Day 3-Day 4 and Day 10-Day 11 ABPM assessments. 1 subject in RMJH-111b arm was discontinued on Day 9 due to meeting protocol-specified criterion (SBP \< 110 mmHg). The SBPs (102-109 mmHg) were not associated with clinical symptoms \& were not assigned as TEAEs.
SBPnight = mean daytime (10 PM to 6 AM) ABPM SBP. Note, mean values of change that are negative represent a decrease in that value from baseline, whereas values that are positive represent an increase. SBPnight was measured twice during the subject's stay at the CRU: baseline measurements were collected from Day 3 to pre-dose Day 4 \& post-dose measurements were collected from Day 10 to Day 11. An Investigational Site staff member placed the cuff on the subject's non-dominant arm \& connected the ABPM at approximately 7 AM (± 60 minutes) on Days 3 \& 10. A pre-dose ABPM reading was recorded immediately prior to the morning dose of run-in period placebo on Day 3 \& the morning dose of treatment period Study Drug (active or placebo) on Day 10. The ABPM was started again immediately after dosing. The ABPM was removed at approximately 8 AM (± 60 minutes) on Days 4 and 11, respectively, but no sooner than 24 hours after the continuous monitoring was initiated.
Outcome measures
| Measure |
RMJH-111b
n=15 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Efficacy of RMJH-111b Compared to Placebo Based on Change From Baseline in SBPnight After 7 Days of Treatment
|
-4.2 mmHg
Standard Deviation 12.54
|
0.7 mmHg
Standard Deviation 12.13
|
SECONDARY outcome
Timeframe: 8 daysPopulation: Efficacy population = all randomized subjects who completed 7 days of treatment \& the Day 3-Day 4 and Day 10-Day 11 ABPM assessments. 1 subject in RMJH-111b arm was discontinued on Day 9 due to meeting protocol-specified criterion (SBP \< 110 mmHg). The SBPs (102-109 mmHg) were not associated with clinical symptoms \& were not assigned as TEAEs.
SBP24hr = mean 24-hour ABPM SBP. Note, mean values of change that are negative represent a decrease in that value from baseline, whereas values that are positive represent an increase. SBP24hr was measured twice during the subject's stay at the CRU: baseline measurements were collected from Day 3 to pre-dose Day 4 \& post-dose measurements were collected from Day 10 to Day 11. An Investigational Site staff member placed the cuff on the subject's non-dominant arm \& connected the ABPM at approximately 7 AM (± 60 minutes) on Days 3 \& 10. A pre-dose ABPM reading was recorded immediately prior to the morning dose of run-in period placebo on Day 3 \& the morning dose of treatment period Study Drug (active or placebo) on Day 10. The ABPM was started again immediately after dosing. The ABPM was removed at approximately 8 AM (± 60 minutes) on Days 4 and 11, respectively, but no sooner than 24 hours after the continuous monitoring was initiated.
Outcome measures
| Measure |
RMJH-111b
n=15 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Efficacy of RMJH-111b Compared to Placebo Based on Change From Baseline in SBP24hr After 7 Days of Treatment
|
-3.8 mmHg
Standard Deviation 11.72
|
2.3 mmHg
Standard Deviation 11.61
|
SECONDARY outcome
Timeframe: 8 daysPopulation: Efficacy population = all randomized subjects who completed 7 days of treatment \& the Day 3-Day 4 and Day 10-Day 11 ABPM assessments. 1 subject in RMJH-111b arm was discontinued on Day 9 due to meeting protocol-specified criterion (SBP \< 110 mmHg). The SBPs (102-109 mmHg) were not associated with clinical symptoms \& were not assigned as TEAEs.
DBPday = mean daytime (8 AM to 4 PM) ABPM DBP. Note, mean values of change that are negative represent a decrease in that value from baseline, whereas values that are positive represent an increase. DBPday was measured twice during the subject's stay at the CRU: baseline measurements were collected from Day 3 to pre-dose Day 4 \& post-dose measurements were collected from Day 10 to Day 11. An Investigational Site staff member placed the cuff on the subject's non-dominant arm \& connected the ABPM at approximately 7 AM (± 60 minutes) on Days 3 \& 10. A pre-dose ABPM reading was recorded immediately prior to the morning dose of run-in period placebo on Day 3 \& the morning dose of treatment period Study Drug (active or placebo) on Day 10. The ABPM was started again immediately after dosing. The ABPM was removed at approximately 8 AM (± 60 minutes) on Days 4 and 11, respectively, but no sooner than 24 hours after the continuous monitoring was initiated.
Outcome measures
| Measure |
RMJH-111b
n=15 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Efficacy of RMJH-111b Compared to Placebo Based on Change From Baseline in DBPday After 7 Days of Treatment
|
-3.5 mmHg
Standard Deviation 6.88
|
-1.2 mmHg
Standard Deviation 7.12
|
SECONDARY outcome
Timeframe: 8 daysPopulation: Efficacy population = all randomized subjects who completed 7 days of treatment \& the Day 3-Day 4 and Day 10-Day 11 ABPM assessments. 1 subject in RMJH-111b arm was discontinued on Day 9 due to meeting protocol-specified criterion (SBP \< 110 mmHg). The SBPs (102-109 mmHg) were not associated with clinical symptoms \& were not assigned as TEAEs.
DBPnight = mean nighttime (10 PM to 6 AM) ABPM DBP. Note, mean values of change that are negative represent a decrease in that value from baseline, whereas values that are positive represent an increase. DBPnight was measured twice during the subject's stay at the CRU: baseline measurements were collected from Day 3 to pre-dose Day 4 \& post-dose measurements were collected from Day 10 to Day 11. An Investigational Site staff member placed the cuff on the subject's non-dominant arm \& connected the ABPM at approximately 7 AM (± 60 minutes) on Days 3 \& 10. A pre-dose ABPM reading was recorded immediately prior to the morning dose of run-in period placebo on Day 3 \& the morning dose of treatment period Study Drug (active or placebo) on Day 10. The ABPM was started again immediately after dosing. The ABPM was removed at approximately 8 AM (± 60 minutes) on Days 4 and 11, respectively, but no sooner than 24 hours after the continuous monitoring was initiated.
Outcome measures
| Measure |
RMJH-111b
n=15 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Efficacy of RMJH-111b Compared to Placebo Based on Change From Baseline in DBPnight After 7 Days of Treatment
|
-1.9 mmHg
Standard Deviation 8.76
|
-0.6 mmHg
Standard Deviation 7.46
|
SECONDARY outcome
Timeframe: 8 daysPopulation: Efficacy population = all randomized subjects who completed 7 days of treatment \& the Day 3-Day 4 and Day 10-Day 11 ABPM assessments. 1 subject in RMJH-111b arm was discontinued on Day 9 due to meeting protocol-specified criterion (SBP \< 110 mmHg). The SBPs (102-109 mmHg) were not associated with clinical symptoms \& were not assigned as TEAEs.
DBP24hr = mean 24-hour ABPM DBP. Note, mean values of change that are negative represent a decrease in that value from baseline, whereas values that are positive represent an increase. DBP24hr was measured twice during the subject's stay at the CRU: baseline measurements were collected from Day 3 to pre-dose Day 4 \& post-dose measurements were collected from Day 10 to Day 11. An Investigational Site staff member placed the cuff on the subject's non-dominant arm \& connected the ABPM at approximately 7 AM (± 60 minutes) on Days 3 \& 10. A pre-dose ABPM reading was recorded immediately prior to the morning dose of run-in period placebo on Day 3 \& the morning dose of treatment period Study Drug (active or placebo) on Day 10. The ABPM was started again immediately after dosing. The ABPM was removed at approximately 8 AM (± 60 minutes) on Days 4 and 11, respectively, but no sooner than 24 hours after the continuous monitoring was initiated.
Outcome measures
| Measure |
RMJH-111b
n=15 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Efficacy of RMJH-111b Compared to Placebo Based on Change From Baseline in DBP24hr After 7 Days of Treatment
|
-2.3 mmHg
Standard Deviation 6.97
|
0.3 mmHg
Standard Deviation 6.53
|
SECONDARY outcome
Timeframe: 7 daysPopulation: Efficacy population = all randomized subjects who completed 7 days of treatment \& pre-dose Day 4 \& Day 11 assessments. 1 subject in RMJH-111b arm was discontinued on Day 9 for meeting protocol-specified criterion \[SBP\<110 mmHg; SBPs (102-109 mmHg) were not associated with clinical symptoms \& not assigned as TEAEs\] \& is therefore excluded.
Change from baseline (pre-dose Day 4) in seated SBP after 7 days of treatment (Day 11) with RMJH-111b compared to placebo was a secondary efficacy variable (i.e., seated SBP served dual functions as safety and efficacy variables, with the safety population used for the safety analyses described in outcome 3 and the efficacy population used for the efficacy analyses described here). Note, mean values that are negative represent a decrease in that value from baseline, whereas values that are positive represent an increase.
Outcome measures
| Measure |
RMJH-111b
n=15 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Efficacy of RMJH-111b Compared to Placebo Based on Change From Baseline in Seated SBP After 7 Days of Treatment
|
-14.6 mmHg
Standard Deviation 13.58
|
-7.2 mmHg
Standard Deviation 7.36
|
SECONDARY outcome
Timeframe: 7 daysPopulation: Efficacy population = all randomized subjects who completed 7 days of treatment \& pre-dose Day 4 \& Day 11 assessments. 1 subject in RMJH-111b arm was discontinued on Day 9 for meeting protocol-specified criterion \[SBP\<110 mmHg; SBPs (102-109 mmHg) were not associated with clinical symptoms \& not assigned as TEAEs\] \& is therefore excluded.
Change from baseline (pre-dose Day 4) in seated DBP after 7 days of treatment (Day 11) with RMJH-111b compared to placebo was a secondary efficacy variable (i.e., seated DBP served dual functions as safety and efficacy variables, with the safety population used for the safety analyses described in outcome 3 and the efficacy population used for the efficacy analyses described here). Note, mean values that are negative represent a decrease in that value from baseline, whereas values that are positive represent an increase.
Outcome measures
| Measure |
RMJH-111b
n=15 Participants
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 Participants
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Efficacy of RMJH-111b Compared to Placebo Based on Change From Baseline in Seated DBP After 7 Days of Treatment
|
-6.4 mmHg
Standard Deviation 6.08
|
-2.3 mmHg
Standard Deviation 6.25
|
Adverse Events
RMJH-111b
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
RMJH-111b
n=16 participants at risk
Four (4) RMJH-111b (magnesium citrate, tribasic anhydrous) soft gelatin capsules (110 mg elemental magnesium/capsule) orally bid for 7 days
|
Placebo
n=6 participants at risk
Four (4) placebo soft gelatin capsules (0 mg elemental magnesium/capsule) orally bid for 7 days
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.2%
1/16 • Number of events 1 • 14 +/- 3 days. Treatment emergent adverse events (TEAEs) were defined as any adverse event (AE) that started or increased in severity after the first randomized dose of Study Drug (active or placebo) on Day 4 through the Final Study Visit (8 +/-3 days after last randomized dose).
AE = any untoward medical occurrence associated with use of Study Drug (active or placebo), whether or not considered drug related. Includes any unfavorable \& unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of the drug, \& does not imply any judgment about causality. Can arise with any use of the drug (e.g., off-label use, use in combination with another drug) \& any route of administration, formulation, or dose, including overdose.
|
0.00%
0/6 • 14 +/- 3 days. Treatment emergent adverse events (TEAEs) were defined as any adverse event (AE) that started or increased in severity after the first randomized dose of Study Drug (active or placebo) on Day 4 through the Final Study Visit (8 +/-3 days after last randomized dose).
AE = any untoward medical occurrence associated with use of Study Drug (active or placebo), whether or not considered drug related. Includes any unfavorable \& unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of the drug, \& does not imply any judgment about causality. Can arise with any use of the drug (e.g., off-label use, use in combination with another drug) \& any route of administration, formulation, or dose, including overdose.
|
|
Gastrointestinal disorders
Constipation
|
6.2%
1/16 • Number of events 1 • 14 +/- 3 days. Treatment emergent adverse events (TEAEs) were defined as any adverse event (AE) that started or increased in severity after the first randomized dose of Study Drug (active or placebo) on Day 4 through the Final Study Visit (8 +/-3 days after last randomized dose).
AE = any untoward medical occurrence associated with use of Study Drug (active or placebo), whether or not considered drug related. Includes any unfavorable \& unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of the drug, \& does not imply any judgment about causality. Can arise with any use of the drug (e.g., off-label use, use in combination with another drug) \& any route of administration, formulation, or dose, including overdose.
|
0.00%
0/6 • 14 +/- 3 days. Treatment emergent adverse events (TEAEs) were defined as any adverse event (AE) that started or increased in severity after the first randomized dose of Study Drug (active or placebo) on Day 4 through the Final Study Visit (8 +/-3 days after last randomized dose).
AE = any untoward medical occurrence associated with use of Study Drug (active or placebo), whether or not considered drug related. Includes any unfavorable \& unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of the drug, \& does not imply any judgment about causality. Can arise with any use of the drug (e.g., off-label use, use in combination with another drug) \& any route of administration, formulation, or dose, including overdose.
|
|
Gastrointestinal disorders
Diarrhoea
|
12.5%
2/16 • Number of events 2 • 14 +/- 3 days. Treatment emergent adverse events (TEAEs) were defined as any adverse event (AE) that started or increased in severity after the first randomized dose of Study Drug (active or placebo) on Day 4 through the Final Study Visit (8 +/-3 days after last randomized dose).
AE = any untoward medical occurrence associated with use of Study Drug (active or placebo), whether or not considered drug related. Includes any unfavorable \& unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of the drug, \& does not imply any judgment about causality. Can arise with any use of the drug (e.g., off-label use, use in combination with another drug) \& any route of administration, formulation, or dose, including overdose.
|
0.00%
0/6 • 14 +/- 3 days. Treatment emergent adverse events (TEAEs) were defined as any adverse event (AE) that started or increased in severity after the first randomized dose of Study Drug (active or placebo) on Day 4 through the Final Study Visit (8 +/-3 days after last randomized dose).
AE = any untoward medical occurrence associated with use of Study Drug (active or placebo), whether or not considered drug related. Includes any unfavorable \& unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of the drug, \& does not imply any judgment about causality. Can arise with any use of the drug (e.g., off-label use, use in combination with another drug) \& any route of administration, formulation, or dose, including overdose.
|
|
Gastrointestinal disorders
Flatulence
|
6.2%
1/16 • Number of events 1 • 14 +/- 3 days. Treatment emergent adverse events (TEAEs) were defined as any adverse event (AE) that started or increased in severity after the first randomized dose of Study Drug (active or placebo) on Day 4 through the Final Study Visit (8 +/-3 days after last randomized dose).
AE = any untoward medical occurrence associated with use of Study Drug (active or placebo), whether or not considered drug related. Includes any unfavorable \& unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of the drug, \& does not imply any judgment about causality. Can arise with any use of the drug (e.g., off-label use, use in combination with another drug) \& any route of administration, formulation, or dose, including overdose.
|
0.00%
0/6 • 14 +/- 3 days. Treatment emergent adverse events (TEAEs) were defined as any adverse event (AE) that started or increased in severity after the first randomized dose of Study Drug (active or placebo) on Day 4 through the Final Study Visit (8 +/-3 days after last randomized dose).
AE = any untoward medical occurrence associated with use of Study Drug (active or placebo), whether or not considered drug related. Includes any unfavorable \& unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of the drug, \& does not imply any judgment about causality. Can arise with any use of the drug (e.g., off-label use, use in combination with another drug) \& any route of administration, formulation, or dose, including overdose.
|
|
Nervous system disorders
Headache
|
6.2%
1/16 • Number of events 1 • 14 +/- 3 days. Treatment emergent adverse events (TEAEs) were defined as any adverse event (AE) that started or increased in severity after the first randomized dose of Study Drug (active or placebo) on Day 4 through the Final Study Visit (8 +/-3 days after last randomized dose).
AE = any untoward medical occurrence associated with use of Study Drug (active or placebo), whether or not considered drug related. Includes any unfavorable \& unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of the drug, \& does not imply any judgment about causality. Can arise with any use of the drug (e.g., off-label use, use in combination with another drug) \& any route of administration, formulation, or dose, including overdose.
|
16.7%
1/6 • Number of events 2 • 14 +/- 3 days. Treatment emergent adverse events (TEAEs) were defined as any adverse event (AE) that started or increased in severity after the first randomized dose of Study Drug (active or placebo) on Day 4 through the Final Study Visit (8 +/-3 days after last randomized dose).
AE = any untoward medical occurrence associated with use of Study Drug (active or placebo), whether or not considered drug related. Includes any unfavorable \& unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of the drug, \& does not imply any judgment about causality. Can arise with any use of the drug (e.g., off-label use, use in combination with another drug) \& any route of administration, formulation, or dose, including overdose.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.5%
2/16 • Number of events 2 • 14 +/- 3 days. Treatment emergent adverse events (TEAEs) were defined as any adverse event (AE) that started or increased in severity after the first randomized dose of Study Drug (active or placebo) on Day 4 through the Final Study Visit (8 +/-3 days after last randomized dose).
AE = any untoward medical occurrence associated with use of Study Drug (active or placebo), whether or not considered drug related. Includes any unfavorable \& unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of the drug, \& does not imply any judgment about causality. Can arise with any use of the drug (e.g., off-label use, use in combination with another drug) \& any route of administration, formulation, or dose, including overdose.
|
0.00%
0/6 • 14 +/- 3 days. Treatment emergent adverse events (TEAEs) were defined as any adverse event (AE) that started or increased in severity after the first randomized dose of Study Drug (active or placebo) on Day 4 through the Final Study Visit (8 +/-3 days after last randomized dose).
AE = any untoward medical occurrence associated with use of Study Drug (active or placebo), whether or not considered drug related. Includes any unfavorable \& unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of the drug, \& does not imply any judgment about causality. Can arise with any use of the drug (e.g., off-label use, use in combination with another drug) \& any route of administration, formulation, or dose, including overdose.
|
Additional Information
Russell Jaffe, M.D., Chief Executive Officer
RMJ Holdings LLC d/b/a RMJH Rx
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place