A Trial of IW-3718 for 8 Weeks in Patients With Persisten... | NCT03561090

Status Module

Oversight Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
1500 mg IW-3718 BID + PPI	Experimental	Three 500 mg IW-3718 tablets administered twice daily (BID), immediately after the morning and evening meals. Standard-dose PPIs administered QD approximately 30-60 minutes before the morning meal each day.	Drug: IW-3718 Drug: Standard-dose PPIs QD
Placebo + PPI	Placebo Comparator	Three placebo tablets administered BID immediately after the morning and evening meals. Standard-dose PPIs administered QD approximately 30-60 minutes before the morning meal each day.	Drug: placebo Drug: Standard-dose PPIs QD

Name	Type	Description	Arm Group Labels	Other Names
IW-3718	Drug	oral tablet	1500 mg IW-3718 BID + PPI
placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in WHSS at Week 8	The WHSS is defined as the weekly average of the DHSS. The DHSS for a day is the greater of the 2 items assessing heartburn severity (Item #1 "Burning feeling behind the breastbone or in the center of the upper stomach" and Item #2 "Pain behind the breastbone or in the center of the upper stomach"). The DHSS items are assessed on a 5-point ordinal scale, where 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, and 5=Severe; higher scores indicate worse symptoms. A negative change from baseline indicates improvement.	Baseline, Week 8

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Weekly Regurgitation Frequency Score (WRFS) at Week 8	The WRFS is defined as the average of available daily regurgitation frequency scores (DRFS) during a week. DRFS is defined as the maximum score of the 2 items measuring regurgitation from a particular day (Item #6 "Regurgitation [liquid or food moving upwards toward your throat or mouth]" and Item #7 "An acid or bitter taste in the mouth"). The DRFS items are assessed on a 4-point ordinal scale, where 0=Never, 1=Rarely, 2-Sometimes, 3=Often, and 4=Very Often; higher scores indicate worse symptoms. A negative change from baseline indicates improvement.

Eligibility Module

Name	Affiliation	Role
Mike Shetzline, MD, PhD	Chief Medical Officer	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Pinnacle Research Group		Anniston	Alabama	36207	United States
Alabama Medical Group, PC

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo BID + PPI	Three placebo tablets administered BID immediately after the morning and evening meals. Standard-dose proton pump inhibitors (PPIs) administered QD approximately 30-60 minutes before the morning meal each day.
FG001	1500 mg IW-3718 BID + PPI

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 14, 2020	Jul 23, 2021

Arm/Group Information

ID	Title	Description
BG000	Placebo BID + PPI	Three placebo tablets administered BID immediately after the morning and evening meals. Standard-dose PPIs administered QD approximately 30-60 minutes before the morning meal each day.
BG001	1500 mg IW-3718 BID + PPI	Three 500 mg IW-3718 tablets administered BID, immediately after the morning and evening meals. Standard-dose PPIs administered QD approximately 30-60 minutes before the morning meal each day.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

- ParticipantsBG000246
- ParticipantsBG001247
- ParticipantsBG002493

Title	Measurements

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000246 ParticipantsBG001247 ParticipantsBG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000246 ParticipantsBG001247 ParticipantsBG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000246 ParticipantsBG001247 ParticipantsBG002

Erosive Esophagitis (EE) Status, as Randomized

Modified Intent-to-Treat (mITT) Population, which included all participants who 1) were randomized prior to or on 04 August 2020, 2) had received at least 1 dose of study drug, and 3) had at least 1 postbaseline primary efficacy assessment.

Count of Participants

Participants

Title	Denominators	Categories
EE Present	ParticipantsBG000228 ParticipantsBG001227 ParticipantsBG002

Weekly Heartburn Severity Score (WHSS) Category, as Randomized

WHSS=weekly average of Daily Heartburn Severity Score (DHSS). DHSS=the greater of the 2 items assessing heartburn severity (#1=Burning feeling behind the breastbone or in the center of the upper stomach; #2=Pain behind the breastbone or in the center of the upper stomach), where 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, and 5=Severe; higher scores indicate worse symptoms.

Baseline is derived from the daily eDiary data collected in the pretreatment period, specifically the period of time from 7 days before randomization up to the time of randomization.

mITT Population, which included all participants who 1) were randomized prior to or on 04 August 2020, 2) had received at least 1 dose of study drug, and 3) had at least 1 postbaseline primary efficacy assessment.

Count of Participants

Participants

Title	Denominators	Categories
WHSS Score >/= 3	ParticipantsBG000228 ParticipantsBG001

WHSS

Baseline is derived from the daily eDiary data collected in the pretreatment period, specifically the period of time from 7 days before randomization up to the time of randomization.

mITT Population: participants who were randomized prior to or on 04 August 2020, and who received at least 1 dose of study drug and had at least 1 postbaseline primary efficacy assessment.

Mean

Standard Deviation

score on a scale

Title	Denominators	Categories
	ParticipantsBG000228 ParticipantsBG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in WHSS at Week 8

The WHSS is defined as the weekly average of the DHSS. The DHSS for a day is the greater of the 2 items assessing heartburn severity (Item #1 "Burning feeling behind the breastbone or in the center of the upper stomach" and Item #2 "Pain behind the breastbone or in the center of the upper stomach"). The DHSS items are assessed on a 5-point ordinal scale, where 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, and 5=Severe; higher scores indicate worse symptoms. A negative change from baseline indicates improvement.

mITT Population: participants who were randomized prior to or on 04 August 2020, and who received at least 1 dose of study drug and had at least 1 postbaseline primary efficacy assessment.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline, Week 8

ID	Title	Description
OG000	Placebo BID + PPI	Three placebo tablets administered BID immediately after the morning and evening meals. Standard-dose PPIs administered QD approximately 30-60 minutes before the morning meal each day.
OG001	1500 mg IW-3718 BID + PPI	Three 500 mg IW-3718 tablets administered BID, immediately after the morning and evening meals. Standard-dose PPIs administered QD approximately 30-60 minutes before the morning meal each day.

Units	Counts
Participants	OG000228 OG001227

Title

Denominators

Categories

Title	Measurements
	OG000-1.774± 0.082 OG001-1.719± 0.082

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Treatment difference calculated as least squares mean (LSM) change from baseline at Week 8; IW-3718 - placebo based on an mixed models repeated measures (MMRM) model with week (categorical), treatment group, week-by-treatment group, and week-by-baseline value interactions, baseline esophagitis status (present vs. not present), and baseline WHSS (< 3 vs. ≥ 3) as fixed effect terms and baseline value as a covariate, with subject as a random effect. An unstructured covariance structure was used.	MMRM		0.6346		Least squares (LS) mean difference	0.055			2-Sided	95	-0.172	0.281			Treatment difference (IW-3718 - placebo)

Secondary

Change From Baseline in Weekly Regurgitation Frequency Score (WRFS) at Week 8

The WRFS is defined as the average of available daily regurgitation frequency scores (DRFS) during a week. DRFS is defined as the maximum score of the 2 items measuring regurgitation from a particular day (Item #6 "Regurgitation [liquid or food moving upwards toward your throat or mouth]" and Item #7 "An acid or bitter taste in the mouth"). The DRFS items are assessed on a 4-point ordinal scale, where 0=Never, 1=Rarely, 2-Sometimes, 3=Often, and 4=Very Often; higher scores indicate worse symptoms. A negative change from baseline indicates improvement.

mITT Population: participants who were randomized prior to or on 04 August 2020, and who received at least 1 dose of study drug and had at least 1 postbaseline primary efficacy assessment.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline, Week 8

ID	Title	Description
OG000	Placebo BID + PPI	Three placebo tablets administered BID immediately after the morning and evening meals. Standard-dose PPIs administered QD approximately 30-60 minutes before the morning meal each day.
OG001	1500 mg IW-3718 BID + PPI	Three 500 mg IW-3718 tablets administered BID, immediately after the morning and evening meals. Standard-dose PPIs administered QD approximately 30-60 minutes before the morning meal each day.

Secondary

Percentage of Participants Who Were Overall Heartburn Responders During the 8-Week Treatment Period

An overall heartburn responder is a participant who is a weekly heartburn responder for at least 4 of the 8 treatment weeks and for at least 1 of the final 2 treatment weeks (i.e., Week 7 and Week 8). A weekly heartburn responder is a participant with a decrease of >/= 45% from baseline in WHSS. A participant who reported heartburn severity for less than 4 days during a week is not considered a responder for that week.

mITT Population: participants who were randomized prior to or on 04 August 2020, and who received at least 1 dose of study drug and had at least 1 postbaseline primary efficacy assessment.

Posted

Number

95% Confidence Interval

percentage of participants

Up to Week 8

ID	Title	Description
OG000	Placebo BID + PPI	Three placebo tablets administered BID immediately after the morning and evening meals. Standard-dose PPIs administered QD approximately 30-60 minutes before the morning meal each day.
OG001

Secondary

Proportion of Heartburn-Free Days During the 8-Week Treatment Period

Proportion of heartburn-free days is calculated as the number of heartburn-free (DHSS=0) days divided by the number of diary entry days. The DHSS for a day is the greater of the 2 items assessing heartburn severity (Item #1 "Burning feeling behind the breastbone or in the center of the upper stomach" and Item #2 "Pain behind the breastbone or in the center of the upper stomach"). The DHSS items are assessed on a 5-point ordinal scale, where 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, and 5=Severe; higher scores indicate worse symptoms. A negative change from baseline indicates improvement

mITT Population: participants who were randomized prior to or on 04 August 2020, and who received at least 1 dose of study drug and had at least 1 postbaseline primary efficacy assessment.

Posted

Mean

Standard Error

proportion of days

Up to Week 8

ID	Title	Description
OG000	Placebo BID + PPI	Three placebo tablets administered BID, immediately after the morning and evening meals. Standard-dose PPIs administered QD approximately 30-60 minutes before the morning meal each day.
OG001	1500 mg IW-3718 BID + PPI	Three 1500 mg IW-3718 tablets administered BID immediately after the morning and evening meals. Standard-dose PPIs administered QD approximately 30-60 minutes before the morning meal each day.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo BID + PPI	Three placebo tablets administered BID, immediately after the morning and evening meals. Standard-dose PPIs administered QD approximately 30-60 minutes before the morning meal each day.	0	246	0	246	37	246
EG001	1500 mg IW-3718 BID + PPI	Three 1500 mg IW-3718 tablets administered BID immediately after the morning and evening meals. Standard-dose PPIs administered QD approximately 30-60 minutes before the morning meal each day.	0	247	3	247	37	247

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cholecystitis	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected246 at risk EG0011 affected247 at risk
COVID-19	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected246 at risk EG0011 affected247 at risk
Carbon monoxide poisoning	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected246 at risk EG0011 affected247 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Flatulence	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG00010 affected246 at risk EG0019 affected247 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG00017 affected246 at risk EG0018 affected247 at risk
Constipation	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0003 affected246 at risk EG0016 affected247 at risk
Nausea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0006 affected246 at risk EG0016 affected247 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected246 at risk EG0015 affected247 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected246 at risk EG0018 affected247 at risk
Nasopharyngitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0002 affected246 at risk EG0015 affected247 at risk
Urinary tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0002 affected246 at risk EG0015 affected247 at risk

ID	Term
D015154	Esophageal Motility Disorders
D003680	Deglutition Disorders
D004935	Esophageal Diseases
D005767	Gastrointestinal Diseases
D004066	Digestive System Diseases