Trial Outcomes & Findings for Trial of a Gastrin Receptor Antagonist in Barrett's Esophagus (NCT NCT01298999)
NCT ID: NCT01298999
Last Updated: 2021-11-23
Results Overview
The study is designed to examine change in tissue Ki67 expression, a marker of cellular proliferation.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
27 participants
Primary outcome timeframe
Up to 3 months from baseline
Results posted on
2021-11-23
Participant Flow
3 subjects were screen failures. 24 out of 27 subjects were randomized.
Participant milestones
| Measure |
YF476
YF476 (gastrin-receptor antagonist)
YF476: 25 mg: one capsule to be taken by mouth once daily for 12 weeks.
|
Placebo
Placebo pill (identical in appearance to YF476 pills)
Placebo: Matching placebo: one capsule to be taken by mouth once daily for 12 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
13
|
11
|
|
Overall Study
COMPLETED
|
10
|
10
|
|
Overall Study
NOT COMPLETED
|
3
|
1
|
Reasons for withdrawal
| Measure |
YF476
YF476 (gastrin-receptor antagonist)
YF476: 25 mg: one capsule to be taken by mouth once daily for 12 weeks.
|
Placebo
Placebo pill (identical in appearance to YF476 pills)
Placebo: Matching placebo: one capsule to be taken by mouth once daily for 12 weeks.
|
|---|---|---|
|
Overall Study
Physician Decision
|
0
|
1
|
|
Overall Study
Baseline Endoscopy showed low grade dysplasia or indefinite for dysplasia
|
3
|
0
|
Baseline Characteristics
Arms analyzed separately.
Baseline characteristics by cohort
| Measure |
YF476
n=13 Participants
YF476 (gastrin-receptor antagonist)
YF476: 25 mg: one capsule to be taken by mouth once daily for 12 weeks.
|
Placebo
n=11 Participants
Placebo pill (identical in appearance to YF476 pills)
Placebo: Matching placebo: one capsule to be taken by mouth once daily for 12 weeks.
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
64.4 years
STANDARD_DEVIATION 7.2 • n=13 Participants
|
68.6 years
STANDARD_DEVIATION 6.6 • n=11 Participants
|
66.3 years
STANDARD_DEVIATION 7.1 • n=24 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=13 Participants
|
1 Participants
n=11 Participants
|
3 Participants
n=24 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=13 Participants
|
10 Participants
n=11 Participants
|
21 Participants
n=24 Participants
|
|
Race/Ethnicity, Customized
Race, white
|
13 Participants
n=13 Participants
|
11 Participants
n=11 Participants
|
24 Participants
n=24 Participants
|
|
BMI
|
28.9 kg/m2
STANDARD_DEVIATION 4.7 • n=13 Participants
|
26.7 kg/m2
STANDARD_DEVIATION 3.1 • n=11 Participants
|
27.9 kg/m2
STANDARD_DEVIATION 4.1 • n=24 Participants
|
|
Waist circumference
|
95.7 cm
STANDARD_DEVIATION 17.8 • n=13 Participants
|
98.1 cm
STANDARD_DEVIATION 10.9 • n=11 Participants
|
96.8 cm
STANDARD_DEVIATION 14.8 • n=24 Participants
|
|
Current smoker
|
0 Participants
n=13 Participants
|
0 Participants
n=11 Participants
|
0 Participants
n=24 Participants
|
|
Proton Pump Inhibitor (PPI) frequency
Once daily
|
8 Participants
n=13 Participants
|
6 Participants
n=11 Participants
|
14 Participants
n=24 Participants
|
|
Proton Pump Inhibitor (PPI) frequency
Twice daily
|
5 Participants
n=13 Participants
|
5 Participants
n=11 Participants
|
10 Participants
n=24 Participants
|
|
Aspirin Use
|
3 Participants
n=13 Participants
|
2 Participants
n=11 Participants
|
5 Participants
n=24 Participants
|
|
Barrett's Esophagus length
YF476
|
3 cm
n=13 Participants • Arms analyzed separately.
|
—
|
3 cm
n=13 Participants • Arms analyzed separately.
|
|
Barrett's Esophagus length
Placebo
|
—
|
6 cm
n=11 Participants • Arms analyzed separately.
|
6 cm
n=11 Participants • Arms analyzed separately.
|
|
Hiatal hernia size
YF476
|
2 cm
n=13 Participants • Arms analyzed separately.
|
—
|
2 cm
n=13 Participants • Arms analyzed separately.
|
|
Hiatal hernia size
Placebo
|
—
|
4 cm
n=11 Participants • Arms analyzed separately.
|
4 cm
n=11 Participants • Arms analyzed separately.
|
|
Serum gastrin
|
60.3 pmol/L
STANDARD_DEVIATION 41.7 • n=13 Participants
|
51.8 pmol/L
STANDARD_DEVIATION 29.1 • n=11 Participants
|
56.4 pmol/L
STANDARD_DEVIATION 36.0 • n=24 Participants
|
|
Plasma CgA
|
12.9 nmol/L
STANDARD_DEVIATION 17.2 • n=13 Participants
|
9.1 nmol/L
STANDARD_DEVIATION 5.0 • n=11 Participants
|
11.2 nmol/L
STANDARD_DEVIATION 13.0 • n=24 Participants
|
PRIMARY outcome
Timeframe: Up to 3 months from baselinePopulation: Analysis limited to those who completed study (10 subjects in the intervention group and 10 subjects in the placebo group).
The study is designed to examine change in tissue Ki67 expression, a marker of cellular proliferation.
Outcome measures
| Measure |
YF476
n=10 Participants
YF476 (gastrin-receptor antagonist)
YF476: 25 mg: one capsule to be taken by mouth once daily for 12 weeks.
|
Placebo
n=10 Participants
Placebo pill (identical in appearance to YF476 pills)
Placebo: Matching placebo: one capsule to be taken by mouth once daily for 12 weeks.
|
|---|---|---|
|
Mean Ki67 Expression
|
35.6 cells/mm2
Standard Deviation 620.7
|
307.8 cells/mm2
Standard Deviation 640.3
|
PRIMARY outcome
Timeframe: Up to 3 months from baselinePopulation: Analysis limited to those who completed study (10 subjects in the intervention group and 10 subjects in the placebo group).
Participants with changes in gene expression were assessed by RNA-sequencing (i.e., sample has sufficient RNA for analysis) between baseline and up to 3 months are tallied.
Outcome measures
| Measure |
YF476
n=10 Participants
YF476 (gastrin-receptor antagonist)
YF476: 25 mg: one capsule to be taken by mouth once daily for 12 weeks.
|
Placebo
n=10 Participants
Placebo pill (identical in appearance to YF476 pills)
Placebo: Matching placebo: one capsule to be taken by mouth once daily for 12 weeks.
|
|---|---|---|
|
Number of Participants That Experienced Change in Any Biomarker Expression
|
10 Participants
|
9 Participants
|
SECONDARY outcome
Timeframe: Up to 4 months from baselineA measure of safety and tolerability. Participants with recorded adverse events were tallied. The events include any adverse events and/or severe adverse events.
Outcome measures
| Measure |
YF476
n=13 Participants
YF476 (gastrin-receptor antagonist)
YF476: 25 mg: one capsule to be taken by mouth once daily for 12 weeks.
|
Placebo
n=11 Participants
Placebo pill (identical in appearance to YF476 pills)
Placebo: Matching placebo: one capsule to be taken by mouth once daily for 12 weeks.
|
|---|---|---|
|
Number of Participants That Experienced Adverse Events
Serious Adverse Event
|
1 Participants
|
0 Participants
|
|
Number of Participants That Experienced Adverse Events
Any Adverse Event
|
10 Participants
|
7 Participants
|
Adverse Events
YF476
Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
YF476
n=13 participants at risk
YF476 (gastrin-receptor antagonist)
YF476: 25 mg: one capsule to be taken by mouth once daily for 12 weeks.
|
Placebo
n=11 participants at risk
Placebo pill (identical in appearance to YF476 pills)
Placebo: Matching placebo: one capsule to be taken by mouth once daily for 12 weeks.
|
|---|---|---|
|
Reproductive system and breast disorders
Scrotal abscess
|
7.7%
1/13 • Number of events 1 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
0.00%
0/11 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
Other adverse events
| Measure |
YF476
n=13 participants at risk
YF476 (gastrin-receptor antagonist)
YF476: 25 mg: one capsule to be taken by mouth once daily for 12 weeks.
|
Placebo
n=11 participants at risk
Placebo pill (identical in appearance to YF476 pills)
Placebo: Matching placebo: one capsule to be taken by mouth once daily for 12 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
23.1%
3/13 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
9.1%
1/11 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
|
Gastrointestinal disorders
Abdominal pain
|
15.4%
2/13 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
18.2%
2/11 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/13 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
9.1%
1/11 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
|
Gastrointestinal disorders
Nausea
|
7.7%
1/13 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
9.1%
1/11 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
|
Gastrointestinal disorders
Rectal bleeding
|
7.7%
1/13 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
9.1%
1/11 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
|
Gastrointestinal disorders
Acid reflux
|
0.00%
0/13 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
9.1%
1/11 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/13 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
9.1%
1/11 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
|
Nervous system disorders
Headache
|
23.1%
3/13 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
27.3%
3/11 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
|
Respiratory, thoracic and mediastinal disorders
Nasopharyngitis
|
15.4%
2/13 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
18.2%
2/11 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
|
Skin and subcutaneous tissue disorders
Rash
|
15.4%
2/13 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
9.1%
1/11 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
|
Nervous system disorders
Dizziness
|
15.4%
2/13 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
9.1%
1/11 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/13 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
18.2%
2/11 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/13 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
18.2%
2/11 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.7%
1/13 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
0.00%
0/11 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
|
General disorders
Fatigue
|
7.7%
1/13 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
0.00%
0/11 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
|
General disorders
Fever
|
7.7%
1/13 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
0.00%
0/11 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
|
General disorders
Chest pain
|
7.7%
1/13 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
0.00%
0/11 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
|
General disorders
Epistaxis
|
0.00%
0/13 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
9.1%
1/11 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
|
Endocrine disorders
Hypoglycemia
|
7.7%
1/13 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
0.00%
0/11 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
|
General disorders
Mouth ulcer
|
7.7%
1/13 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
0.00%
0/11 • Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place