Trial Outcomes & Findings for A Study to Evaluate the Effect of Camicinal on Gastroparesis Symptoms in Type 1 and 2 Diabetic Subjects With Gastroparesis (NCT NCT02210000)

Last Updated: 2017-12-11

Results Overview

The GCSI-DD consists of nine symptom severity items covering the following domains: nausea/vomiting; fullness/early satiety, and bloating. In addition, the GCSI-DD contains two symptom severity items upper abdominal pain and overall rating of gastroparesis symptoms. Participants were asked to rate each symptom on a 6-point scale from 0 to 5 with lower scores representing less symptom severity and higher scores indicating more severe symptoms. Fullness/early satiety response is defined as an improvement from Baseline by at least one point in the weekly average for the subscale. A participant was defined as a responder if the participant's weekly average change from Baseline in the fullness/early satiety response score improved by at least 1 point. Percentage of participants showing response were presented.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

114 participants

Primary outcome timeframe

Week 12

Results posted on

2017-12-11

Participant Flow

This study was conducted from 27 August 2014 till 24 August 2015 across 34 centers in the united states (US). A total of 120 participants with gastroparesis and Type 1 or 2 diabetes mellitus were planned to be enrolled.

A total of 387 participants with gastroparesis and Type 1 or 2 diabetes mellitus were screened, of which 273 participants did not meet the inclusion/exclusion criteria and thus, were screen failures. A total of 114 participants were randomized in the study. Participants started recording GCSI-DD for 7 days post-screening to assess baseline symptoms

Participant milestones

Participant milestones
Measure	CAMICINAL 25 MG Eligible participants received oral Camicinal 25 milligrams (mg) once daily in the morning with 100 milliliter (mL) of water up to 84 days and were followed-up for 2 weeks.	PLACEBO Eligible participants received oral matching Placebo once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.
Overall Study STARTED	57	57
Overall Study COMPLETED	38	36
Overall Study NOT COMPLETED	19	21

Reasons for withdrawal

Reasons for withdrawal
Measure	CAMICINAL 25 MG Eligible participants received oral Camicinal 25 milligrams (mg) once daily in the morning with 100 milliliter (mL) of water up to 84 days and were followed-up for 2 weeks.	PLACEBO Eligible participants received oral matching Placebo once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.
Overall Study Study Terminated	11	12
Overall Study Withdrawal by Subject	7	1
Overall Study Adverse Event	1	5
Overall Study Lost to Follow-up	0	2
Overall Study Physician Decision	0	1

Baseline Characteristics

A Study to Evaluate the Effect of Camicinal on Gastroparesis Symptoms in Type 1 and 2 Diabetic Subjects With Gastroparesis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CAMICINAL 25 MG n=58 Participants Eligible participants received oral Camicinal 25 mg once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.	PLACEBO n=56 Participants Eligible participants received oral matching Placebo once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.	Total n=114 Participants Total of all reporting groups
Age, Continuous	57.3 Years STANDARD_DEVIATION 12.47 • n=5 Participants	58.3 Years STANDARD_DEVIATION 9.81 • n=7 Participants	57.8 Years STANDARD_DEVIATION 11.20 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	20 Participants n=7 Participants	36 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants	36 Participants n=7 Participants	78 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants	15 Participants n=7 Participants	27 Participants n=5 Participants
Race (NIH/OMB) White	44 Participants n=5 Participants	40 Participants n=7 Participants	84 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

PRIMARY outcome

Timeframe: Week 12

Population: Intent-to-treat (ITT) Population comprised of all randomized participants.

Outcome measures

Outcome measures
Measure	CAMICINAL 25 MG n=57 Participants Eligible participants received oral Camicinal 25 mg once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.	PLACEBO n=57 Participants Eligible participants received oral matching Placebo once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.
Percentage of Responders Based on the Fullness/Early Satiety Subscale (Responders) as Assessed by Gastrointestinal Cardinal Symptom Index-Daily Diary (GCSI-DD) at Week 12	26.32 Percentage of responders	42.11 Percentage of responders

SECONDARY outcome

Timeframe: Baseline (Screening) and Week 12

Population: ITT Population. Only those participants available at the time of assessment were included in the analysis.

Items of GCSI-DD for gastroparesis (GP) symptom assessment included: 3-nausea, 4-feeling full after meals, 5-bloating, 6-unable to finish normal meal, 7-retching, 8-vomiting, 9-stomach visibly larger, 10-stomach fullness, 11-loss of appetite, 12-upper abdominal pain, 13-upper abdominal discomfort and 14-overall severity of GP symptoms. Each symptom rated on a 6-point scale from 0 to 5 where 0 indicated absence of symptom and higher score indicated greater severity of symptom. Score of nausea/vomiting subscale was mean of items 3, 7, 8; fullness/early satiety subscale was mean of items 4, 6, 10, 11; bloating subscale was mean of items 5, 9. Total GCSI-DD score was mean of 3 subscales. For all, 0 indicated absence of symptom and higher score indicated greater severity of symptoms. Baseline was defined as weekly average of last 7 daily scores recorded during screening period. Change from Baseline was calculated by subtracting mean score for Baseline from weekly average score of Week 12.

Outcome measures

Outcome measures
Measure	CAMICINAL 25 MG n=57 Participants Eligible participants received oral Camicinal 25 mg once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.	PLACEBO n=57 Participants Eligible participants received oral matching Placebo once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.
Change From Baseline in Individual Items, Subscales and Total Score of GCSI-DD at Week 12 Nausea	-1.250 Scores on a scale Standard Error 0.1714	-1.460 Scores on a scale Standard Error 0.1765
Change From Baseline in Individual Items, Subscales and Total Score of GCSI-DD at Week 12 Feeling full after meals	-1.063 Scores on a scale Standard Error 0.2102	-1.812 Scores on a scale Standard Error 0.2146
Change From Baseline in Individual Items, Subscales and Total Score of GCSI-DD at Week 12 Bloating	-1.382 Scores on a scale Standard Error 0.2227	-1.871 Scores on a scale Standard Error 0.2270
Change From Baseline in Individual Items, Subscales and Total Score of GCSI-DD at Week 12 Unable to finish normal meal	-0.876 Scores on a scale Standard Error 0.1819	-1.373 Scores on a scale Standard Error 0.1858
Change From Baseline in Individual Items, Subscales and Total Score of GCSI-DD at Week 12 Retching	-0.894 Scores on a scale Standard Error 0.1517	-0.944 Scores on a scale Standard Error 0.1554
Change From Baseline in Individual Items, Subscales and Total Score of GCSI-DD at Week 12 Vomiting	-0.532 Scores on a scale Standard Error 0.1112	-0.494 Scores on a scale Standard Error 0.1144
Change From Baseline in Individual Items, Subscales and Total Score of GCSI-DD at Week 12 Stomach visiblly larger	-0.998 Scores on a scale Standard Error 0.2124	-1.473 Scores on a scale Standard Error 0.2165
Change From Baseline in Individual Items, Subscales and Total Score of GCSI-DD at Week 12 Stomach fullness	-1.200 Scores on a scale Standard Error 0.2090	-1.661 Scores on a scale Standard Error 0.2124
Change From Baseline in Individual Items, Subscales and Total Score of GCSI-DD at Week 12 Loss of appetite	-0.930 Scores on a scale Standard Error 0.1732	-1.465 Scores on a scale Standard Error 0.1774
Change From Baseline in Individual Items, Subscales and Total Score of GCSI-DD at Week 12 Upper abdominal pain	-1.186 Scores on a scale Standard Error 0.1887	-1.383 Scores on a scale Standard Error 0.1922
Change From Baseline in Individual Items, Subscales and Total Score of GCSI-DD at Week 12 Upper abdominal discomfort	-1.304 Scores on a scale Standard Error 0.2051	-1.618 Scores on a scale Standard Error 0.2097
Change From Baseline in Individual Items, Subscales and Total Score of GCSI-DD at Week 12 Overall severity of GP	-1.173 Scores on a scale Standard Error 0.1626	-1.557 Scores on a scale Standard Error 0.1667
Change From Baseline in Individual Items, Subscales and Total Score of GCSI-DD at Week 12 Nausea/vomiting subscale	-0.888 Scores on a scale Standard Error 0.1183	-0.956 Scores on a scale Standard Error 0.1216
Change From Baseline in Individual Items, Subscales and Total Score of GCSI-DD at Week 12 Fullness/Early Satiety Subscale	-1.041 Scores on a scale Standard Error 0.1696	-1.589 Scores on a scale Standard Error 0.1725
Change From Baseline in Individual Items, Subscales and Total Score of GCSI-DD at Week 12 Bloating Subscale	-1.189 Scores on a scale Standard Error 0.2115	-1.668 Scores on a scale Standard Error 0.2153
Change From Baseline in Individual Items, Subscales and Total Score of GCSI-DD at Week 12 Total GCSI-DD scale	-1.037 Scores on a scale Standard Error 0.1470	-1.393 Scores on a scale Standard Error 0.1498

SECONDARY outcome

Timeframe: Up to 100 days

Population: Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of Camicinal in blood and therefore was analyzed in the Camicinal group.

Abnormal values of systolic and diastolic blood pressure were measured. If the value for a participant at a given visit was outside the PCI, the participants were further categorized as per the increase or decrease of systolic blood pressure (SBP) and diastolic blood pressure (DBP) from Baseline by 10, 20 and 40 millimeters of mercury (mm of Hg). Number of participants with absolute (ABS) SBP (\>160 mm Hg) and ABS DBP (100 mm Hg) were also analyzed. Change from Baseline (CFB) is the post-Baseline value minus the Baseline value. Participants were counted only once per parameter. Participant may have had more than 1 abnormal parameter. Only worst post-Baseline CFB values were considered. The categories mentioned for data values indicate the blood pressure ranges of clinical concern.

Outcome measures

Outcome measures
Measure	CAMICINAL 25 MG n=58 Participants Eligible participants received oral Camicinal 25 mg once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.	PLACEBO n=56 Participants Eligible participants received oral matching Placebo once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.
Number of Participants With Change From Baseline (Day 1) in Blood Pressure of Potential Clinical Importance (PCI) Over 100 Days SBP, ABS: > 160	4 Participants	5 Participants
Number of Participants With Change From Baseline (Day 1) in Blood Pressure of Potential Clinical Importance (PCI) Over 100 Days SBP, CFB: INCREASE >=20	12 Participants	7 Participants
Number of Participants With Change From Baseline (Day 1) in Blood Pressure of Potential Clinical Importance (PCI) Over 100 Days SBP, CFB: INCREASE >=40	1 Participants	2 Participants
Number of Participants With Change From Baseline (Day 1) in Blood Pressure of Potential Clinical Importance (PCI) Over 100 Days SBP, CFB: DECREASE >=20	9 Participants	11 Participants
Number of Participants With Change From Baseline (Day 1) in Blood Pressure of Potential Clinical Importance (PCI) Over 100 Days SBP, CFB: DECREASE >=40	0 Participants	2 Participants
Number of Participants With Change From Baseline (Day 1) in Blood Pressure of Potential Clinical Importance (PCI) Over 100 Days DBP, ABS: >100	1 Participants	2 Participants
Number of Participants With Change From Baseline (Day 1) in Blood Pressure of Potential Clinical Importance (PCI) Over 100 Days DBP, CFB: INCREASE >=10	13 Participants	10 Participants
Number of Participants With Change From Baseline (Day 1) in Blood Pressure of Potential Clinical Importance (PCI) Over 100 Days DBP, CFB: INCREASE >=20	1 Participants	1 Participants
Number of Participants With Change From Baseline (Day 1) in Blood Pressure of Potential Clinical Importance (PCI) Over 100 Days DBP, CFB: DECREASE >=20	8 Participants	19 Participants
Number of Participants With Change From Baseline (Day 1) in Blood Pressure of Potential Clinical Importance (PCI) Over 100 Days DBP, CFB: DECREASE >=10	3 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 100 days

Population: Safety Population. One participant randomized to Placebo arm had quantifiable concentration of Camicinal in blood and therefore was analyzed in the Camicinal group.

Abnormal values of heart rate over 100 days was analyzed and reported. Participants were counted only once per parameter. Participant may have had more than 1 abnormal parameter. Only worst post baseline CFB values were considered. The categories mentioned for data values indicate the heart rate ranges of clinical concern.

Outcome measures

Outcome measures
Measure	CAMICINAL 25 MG n=58 Participants Eligible participants received oral Camicinal 25 mg once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.	PLACEBO n=56 Participants Eligible participants received oral matching Placebo once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.
Number of Participants With Change From Baseline (Day 1) in Heart Rate of PCI Over 100 Day ABS: >110	1 Participants	1 Participants
Number of Participants With Change From Baseline (Day 1) in Heart Rate of PCI Over 100 Day CFB: INCREASE >=15	4 Participants	4 Participants
Number of Participants With Change From Baseline (Day 1) in Heart Rate of PCI Over 100 Day CFB: INCREASE >=30	0 Participants	2 Participants
Number of Participants With Change From Baseline (Day 1) in Heart Rate of PCI Over 100 Day CFB: DECREASE >=15	5 Participants	7 Participants
Number of Participants With Change From Baseline (Day 1) in Heart Rate of PCI Over 100 Day CFB: DECREASE >=30	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 100 days

Population: Safety Population. One participant randomized to Placebo arm had quantifiable concentration of Camicinal in blood and therefore was analyzed in the Camicinal group.

The 12-lead ECG was analyzed as a measure of safety and tolerability. Number of participants with normal ECG, abnormal clinically significant, and abnormal clinically not significant ECG were reported. PR interval of \< 110 and \> 220 milliseconds (msec), QRS interval of \<75 and \> 110 msec, absolute QTc interval of \> 450 to ≤ 480 or \> 480 to ≤ 500 or \>500 msec, and increase from Baseline in QTc of \> 30 to ≤ 60 msec or \>60 msec was considered as of abnormal.

Outcome measures

Outcome measures
Measure	CAMICINAL 25 MG n=58 Participants Eligible participants received oral Camicinal 25 mg once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.	PLACEBO n=56 Participants Eligible participants received oral matching Placebo once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.
Number of Participants With Normal and Abnormal 12-lead Electrocardiogram (ECG) Measurements Over 100 Days FOLLOW-UP, ABNORMAL - CLINICALLY SIGNIFICANT	0 Participants	0 Participants
Number of Participants With Normal and Abnormal 12-lead Electrocardiogram (ECG) Measurements Over 100 Days BASELINE, NORMAL	34 Participants	29 Participants
Number of Participants With Normal and Abnormal 12-lead Electrocardiogram (ECG) Measurements Over 100 Days BASELINE, ABNORMAL - NOT CLINICALLY SIGNIFICANT	24 Participants	26 Participants
Number of Participants With Normal and Abnormal 12-lead Electrocardiogram (ECG) Measurements Over 100 Days BASELINE, ABNORMAL - CLINICALLY SIGNIFICANT	0 Participants	1 Participants
Number of Participants With Normal and Abnormal 12-lead Electrocardiogram (ECG) Measurements Over 100 Days DAY 14, NORMAL	32 Participants	25 Participants
Number of Participants With Normal and Abnormal 12-lead Electrocardiogram (ECG) Measurements Over 100 Days DAY 14, ABNORMAL - NOT CLINICALLY SIGNIFICANT	22 Participants	25 Participants
Number of Participants With Normal and Abnormal 12-lead Electrocardiogram (ECG) Measurements Over 100 Days DAY 14, ABNORMAL - CLINICALLY SIGNIFICANT	0 Participants	0 Participants
Number of Participants With Normal and Abnormal 12-lead Electrocardiogram (ECG) Measurements Over 100 Days DAY 28, NORMAL	24 Participants	22 Participants
Number of Participants With Normal and Abnormal 12-lead Electrocardiogram (ECG) Measurements Over 100 Days DAY 28, ABNORMAL - NOT CLINICALLY SIGNIFICANT	28 Participants	24 Participants
Number of Participants With Normal and Abnormal 12-lead Electrocardiogram (ECG) Measurements Over 100 Days DAY 28, ABNORMAL - CLINICALLY SIGNIFICANT	0 Participants	0 Participants
Number of Participants With Normal and Abnormal 12-lead Electrocardiogram (ECG) Measurements Over 100 Days DAY 56, NORMAL	19 Participants	23 Participants
Number of Participants With Normal and Abnormal 12-lead Electrocardiogram (ECG) Measurements Over 100 Days DAY 56, ABNORMAL - NOT CLINICALLY SIGNIFICANT	25 Participants	19 Participants
Number of Participants With Normal and Abnormal 12-lead Electrocardiogram (ECG) Measurements Over 100 Days DAY 56, ABNORMAL - CLINICALLY SIGNIFICANT	0 Participants	0 Participants
Number of Participants With Normal and Abnormal 12-lead Electrocardiogram (ECG) Measurements Over 100 Days DAY 84, NORMAL	18 Participants	21 Participants
Number of Participants With Normal and Abnormal 12-lead Electrocardiogram (ECG) Measurements Over 100 Days DAY 84, ABNORMAL - NOT CLINICALLY SIGNIFICANT	20 Participants	15 Participants
Number of Participants With Normal and Abnormal 12-lead Electrocardiogram (ECG) Measurements Over 100 Days DAY 84, ABNORMAL - CLINICALLY SIGNIFICANT	0 Participants	0 Participants
Number of Participants With Normal and Abnormal 12-lead Electrocardiogram (ECG) Measurements Over 100 Days FOLLOW-UP, NORMAL	32 Participants	28 Participants
Number of Participants With Normal and Abnormal 12-lead Electrocardiogram (ECG) Measurements Over 100 Days FOLLOW-UP, ABNORMAL - NOT CLINICALLY SIGNIFICANT	24 Participants	25 Participants

SECONDARY outcome

Timeframe: Up to 100 days

Population: Safety Population. One participant randomized to Placebo arm had quantifiable concentration of Camicinal in blood and therefore was analyzed in the Camicinal group.

Hematology analysis was performed at screening (fasted) and during the study at each indicated time point. Participants with abnormalities in changes from Baseline values were recorded. Total absolute neutrophil count (tANC \<1.5 Giga per Liter \[G/L\]), hemoglobin (\<25 or \>25 G/L), hematocrit (\<0.075 or \>0.075 %), platelet count (\<100 or \>500 G/L), lymphocytes low (\<0.8 G/L), and white blood cells (WBC \<3 G/L or \>20G/L) were analyzed for their low (L) or high (H) values. Change from Baseline (CFB) was the post-Baseline value minus then Baseline value. Baseline was defined as last non-missing measurement prior to dosing. One participant was randomized to Placebo arm; however, was included within the Camicinal treatment group as they reported at least one PK trough concentration \>53 nano-grams per milliliter (ng/mL).

Outcome measures

Outcome measures
Measure	CAMICINAL 25 MG n=58 Participants Eligible participants received oral Camicinal 25 mg once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.	PLACEBO n=56 Participants Eligible participants received oral matching Placebo once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.
Number of Participants With Change From Baseline in Hematological Abnormalities of PCI by Treatment and Visit Over Period tANC, L, <1.5, Day 56	0 Participants	1 Participants
Number of Participants With Change From Baseline in Hematological Abnormalities of PCI by Treatment and Visit Over Period tANC, L, <1.5, Day 100	0 Participants	1 Participants
Number of Participants With Change From Baseline in Hematological Abnormalities of PCI by Treatment and Visit Over Period Hemoglobin, H, CFB >25, Day 56	1 Participants	0 Participants
Number of Participants With Change From Baseline in Hematological Abnormalities of PCI by Treatment and Visit Over Period Hemoglobin, H, CFB >25, Day 84	1 Participants	0 Participants
Number of Participants With Change From Baseline in Hematological Abnormalities of PCI by Treatment and Visit Over Period Hemoglobin, L, CFB < -25, Day 100	1 Participants	0 Participants
Number of Participants With Change From Baseline in Hematological Abnormalities of PCI by Treatment and Visit Over Period Hemoglobin, H, CFB >25, Day 100	1 Participants	0 Participants
Number of Participants With Change From Baseline in Hematological Abnormalities of PCI by Treatment and Visit Over Period Hematocrit, H, >0.54, Day 1	0 Participants	1 Participants
Number of Participants With Change From Baseline in Hematological Abnormalities of PCI by Treatment and Visit Over Period Hematocrit, H, >0.54, Day 28	0 Participants	1 Participants
Number of Participants With Change From Baseline in Hematological Abnormalities of PCI by Treatment and Visit Over Period Hematocrit, H, >0.54, Day 56	0 Participants	1 Participants
Number of Participants With Change From Baseline in Hematological Abnormalities of PCI by Treatment and Visit Over Period Hematocrit, H, CFB >0.075, Day 56	1 Participants	0 Participants
Number of Participants With Change From Baseline in Hematological Abnormalities of PCI by Treatment and Visit Over Period Hematocrit, H, CFB >0.075, Day 84	1 Participants	0 Participants
Number of Participants With Change From Baseline in Hematological Abnormalities of PCI by Treatment and Visit Over Period Hematocrit, L, CFB, >0.54, Day 100	1 Participants	0 Participants
Number of Participants With Change From Baseline in Hematological Abnormalities of PCI by Treatment and Visit Over Period Hematocrit, L, CFB, < -0.075, Day 100	1 Participants	0 Participants
Number of Participants With Change From Baseline in Hematological Abnormalities of PCI by Treatment and Visit Over Period Hematocrit, H, CFB, >0.075, Day 100	1 Participants	0 Participants
Number of Participants With Change From Baseline in Hematological Abnormalities of PCI by Treatment and Visit Over Period Platelet count, L, <100, Day 1	1 Participants	0 Participants
Number of Participants With Change From Baseline in Hematological Abnormalities of PCI by Treatment and Visit Over Period Platelet count, L, <100, Day 28	1 Participants	0 Participants
Number of Participants With Change From Baseline in Hematological Abnormalities of PCI by Treatment and Visit Over Period Platelet count, L, <100, Day 100	1 Participants	0 Participants
Number of Participants With Change From Baseline in Hematological Abnormalities of PCI by Treatment and Visit Over Period Lymphocytes, L, <0.8, Day 1	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 100 days

Population: Safety Population. One participant randomized to Placebo arm had quantifiable concentration of Camicinal in blood and therefore was analyzed in the Camicinal group.

Clinical chemistry laboratory analysis was performed at screening (fasted) and during the study at each indicated time point. Albumin low (\<30 G/L), calcium low (\<2 or \>2.75 millimoles per Liter \[mmol/L\]), creatinine (\>44 micromoles per Liter change from baseline), Glucose (\<3 or \>18 mmol/L), potassium (\<3.0 or \>5.5 mmol/L), sodium (\<130 or \>150 mmol/L), and carbon di oxide (CO2) (\<18 or \>35 mmol/L) were analyzed for their low (L) or high (H) values. Participants with abnormalities in changes from Baseline values were recorded. Change from Baseline is the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	CAMICINAL 25 MG n=58 Participants Eligible participants received oral Camicinal 25 mg once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.	PLACEBO n=56 Participants Eligible participants received oral matching Placebo once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.
Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period Creatinine, H, CFB>44, Day 28	1 Participants	0 Participants
Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period Creatinine, H, CFB>44, Day 56	0 Participants	1 Participants
Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period Creatinine, H, CFB>44, Day 84	2 Participants	2 Participants
Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period Glucose, H, >18, Day 1	1 Participants	3 Participants
Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period Glucose, H, >18, Day 28	1 Participants	4 Participants
Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period Glucose, L, <3.0, Day 56	1 Participants	0 Participants
Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period Glucose, H, >18, Day 56	2 Participants	3 Participants
Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period Glucose, H, >18, Day 84	2 Participants	2 Participants
Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period Glucose, H, >18, Day 100	2 Participants	2 Participants
Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period Potassium, H, >5.5, Day 1	0 Participants	2 Participants
Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period Potassium, H, >5.5, Day 28	2 Participants	0 Participants
Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period Potassium, H, >5.5, Day 56	3 Participants	2 Participants
Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period Potassium, H, >5.5, Day 84	1 Participants	1 Participants
Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period Potassium, H, >5.5, Day 100	1 Participants	0 Participants
Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period Sodium, L, <130, Day 84	1 Participants	0 Participants
Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period Sodium, L, <130, Day 100	0 Participants	1 Participants
Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period Carbon di oxide, L, <18, Day 1	1 Participants	2 Participants
Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period Carbon di oxide, L, <18, Day 28	1 Participants	0 Participants
Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period Carbon di oxide, L, <18, Day 56	1 Participants	0 Participants
Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period Carbon di oxide, L, <18, Day 84	1 Participants	1 Participants
Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period Carbon di oxide, L, <18, Day 100	1 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to end of follow up (100 days)

Population: Safety Population. One participant randomized to Placebo arm had quantifiable concentration of Camicinal in blood and therefore was analyzed in the Camicinal group.

An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Serious adverse event (SAE) is an adverse event that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. Medical events that do not result in death, are not life-threatening, or do not require hospitalization may be considered serious adverse events if they put the participant in danger or require medical or surgical intervention to prevent one of the results listed above. Any AE or SAE that led discontinuation of the study drug either by participant or by investigator was considered as an AE leading to discontinuation of the study drug.

Outcome measures

Outcome measures
Measure	CAMICINAL 25 MG n=58 Participants Eligible participants received oral Camicinal 25 mg once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.	PLACEBO n=56 Participants Eligible participants received oral matching Placebo once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs), and Adverse Events Leading to Discontinuation of the Study Drug WITH ANY AE	28 Participants	35 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs), and Adverse Events Leading to Discontinuation of the Study Drug WITH ANY SAE	3 Participants	2 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs), and Adverse Events Leading to Discontinuation of the Study Drug WITH AE LEADING TO DISCONTINUATION	2 Participants	5 Participants

SECONDARY outcome

Timeframe: Day 28 and Day 84

Population: Safety Population. One participant randomized to Placebo arm had quantifiable concentration of Camicinal in blood and therefore was analyzed in the Camicinal group.

A pre-dose blood sample was collected on Days 28 and 84 for pharmacokinetic analysis. This analysis was applicable only for Camicinal arm and thus, no participants from Placebo arm were analyzed.

Outcome measures

Outcome measures
Measure	CAMICINAL 25 MG n=58 Participants Eligible participants received oral Camicinal 25 mg once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.	PLACEBO Eligible participants received oral matching Placebo once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.
Trough Plasma Concentration of Camicinal on Day 28 and Day 84 DAY 28	171.746 NANOGRAM PER MILLILITER (NG/ML) Standard Deviation 121.7083	—
Trough Plasma Concentration of Camicinal on Day 28 and Day 84 DAY 84	166.382 NANOGRAM PER MILLILITER (NG/ML) Standard Deviation 132.5696	—

Adverse Events

CAMICINAL 25 MG

Serious events: 3 serious events

Other events: 22 other events

Deaths: 0 deaths

PLACEBO

Serious events: 2 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	CAMICINAL 25 MG n=58 participants at risk Eligible participants received oral Camicinal 25 mg once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.	PLACEBO n=56 participants at risk Eligible participants received oral matching Placebo once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.
Ear and labyrinth disorders VERTIGO	1.7% 1/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	0.00% 0/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.
General disorders NON-CARDIAC CHEST PAIN	3.4% 2/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	0.00% 0/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.
Infections and infestations DIVERTICULITIS	0.00% 0/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	1.8% 1/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.
Psychiatric disorders DEPRESSION SUICIDAL	0.00% 0/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	1.8% 1/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	CAMICINAL 25 MG n=58 participants at risk Eligible participants received oral Camicinal 25 mg once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.	PLACEBO n=56 participants at risk Eligible participants received oral matching Placebo once daily in the morning with 100 mL of water up to 84 days and were followed-up for 2 weeks.
Gastrointestinal disorders ABDOMINAL DISTENSION	3.4% 2/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	7.1% 4/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.
Gastrointestinal disorders ABDOMINAL PAIN UPPER	0.00% 0/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	3.6% 2/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.
Gastrointestinal disorders CONSTIPATION	1.7% 1/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	5.4% 3/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.
Gastrointestinal disorders DIARRHOEA	5.2% 3/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	7.1% 4/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.
Gastrointestinal disorders FLATULENCE	3.4% 2/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	1.8% 1/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.
Gastrointestinal disorders NAUSEA	3.4% 2/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	7.1% 4/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.
Gastrointestinal disorders VOMITING	0.00% 0/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	8.9% 5/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.
General disorders FATIGUE	3.4% 2/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	1.8% 1/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.
Infections and infestations BRONCHITIS	0.00% 0/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	3.6% 2/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.
Infections and infestations NASOPHARYNGITIS	5.2% 3/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	1.8% 1/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.
Infections and infestations SINUSITIS	1.7% 1/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	3.6% 2/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.
Infections and infestations TOOTH INFECTION	0.00% 0/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	3.6% 2/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.
Infections and infestations URINARY TRACT INFECTION	0.00% 0/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	3.6% 2/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.
Metabolism and nutrition disorders HYPOGLYCAEMIA	5.2% 3/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	1.8% 1/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.
Musculoskeletal and connective tissue disorders ARTHRALGIA	0.00% 0/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	7.1% 4/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.
Musculoskeletal and connective tissue disorders SYNOVIAL CYST	0.00% 0/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	3.6% 2/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.
Nervous system disorders DIZZINESS	3.4% 2/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	0.00% 0/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.
Nervous system disorders HEADACHE	6.9% 4/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	12.5% 7/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.
Psychiatric disorders DEPRESSION	3.4% 2/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	1.8% 1/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.
Vascular disorders HYPERTENSION	3.4% 2/58 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.	1.8% 1/56 • Up to end of follow up (100 days). Safety Population comprised of participants who received at least one dose of the study drug and were followed-up for at least one post-Baseline safety assessment; however, one participant randomized to Placebo arm had quantifiable concentration of camicinal in blood and therefore was analyzed in the camicinal group.