Trial Outcomes & Findings for Efficacy and Safety of Lubiprostone in Patients With Irritable Bowel Syndrome With Constipation (NCT NCT00380250)

NCT ID: NCT00380250

Last Updated: 2019-11-15

Results Overview

Monthly responder: \>=Moderately relieved symptoms 4 weeks/month or Significantly relieved \>= 2 weeks/month IF: Rescue med use did not increase during the month; AND did not discontinue during the month for lack of efficacy; AND no Moderately worse or Significantly worse response in month. Overall responder: responder for at least 2/3 months

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 590 participants
• Primary outcome timeframe: 12 weeks
• Results posted on: 2019-11-15

Participant Flow

First subject entered 5/12/05; Last subject observation 7/18/08; Multicenter study performed at 65 study sites/centers across the US

Subjects were enrolled after an up to 4 week screening period to meet inclusion/exclusion criteria and randomized on Day 0

Participant milestones

Measure	Lubiprostone Study Period I Subjects who received active drug	Placebo Study Period I Subjects who received placebo
Overall Study STARTED	396	194
Overall Study COMPLETED	297	139
Overall Study NOT COMPLETED	99	55

Reasons for withdrawal

Measure	Lubiprostone Study Period I Subjects who received active drug	Placebo Study Period I Subjects who received placebo
Overall Study Withdrawal by Subject	39	28
Overall Study Adverse Event	20	9
Overall Study Lack of Efficacy	10	8
Overall Study Protocol Violation	15	5
Overall Study Lost to Follow-up	14	5
Overall Study Physician Decision	1	0

Baseline Characteristics

Efficacy and Safety of Lubiprostone in Patients With Irritable Bowel Syndrome With Constipation

Baseline characteristics by cohort

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo	Total n=583 Participants Total of all reporting groups
Age, Continuous	46.7 years n=5 Participants	48.1 years n=7 Participants	47.2 years n=5 Participants
Sex: Female, Male Female	355 Participants n=5 Participants	180 Participants n=7 Participants	535 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	13 Participants n=7 Participants	48 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	0 Participants n=5 Participants	1 Participants n=7 Participants	1 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	53 Participants n=5 Participants	29 Participants n=7 Participants	82 Participants n=5 Participants
Race (NIH/OMB) White	336 Participants n=5 Participants	160 Participants n=7 Participants	496 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	3 Participants n=7 Participants	3 Participants n=5 Participants
Height	64.9 Inches STANDARD_DEVIATION 2.9 • n=5 Participants	64.8 Inches STANDARD_DEVIATION 3.09 • n=7 Participants	64.9 Inches STANDARD_DEVIATION 2.96 • n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: Intent-to-treat (ITT) without Last Observation Carried Forward (LOCF)

Monthly responder: >=Moderately relieved symptoms 4 weeks/month or Significantly relieved >= 2 weeks/month IF:

Rescue med use did not increase during the month; AND did not discontinue during the month for lack of efficacy; AND no Moderately worse or Significantly worse response in month.

Overall responder: responder for at least 2/3 months

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Overall Responder Rate	13.8 percentage of participants	7.8 percentage of participants

SECONDARY outcome

Timeframe: Change from baseline for month 1

Population: ITT with LOCF

SBMs are any bowel movement not associated with rescue medication use.

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 1 Spontaneous Bowel Movement (SBM) Frequency Rates Change From Baseline	1.54 SBM/week Standard Deviation 2.462	1.21 SBM/week Standard Deviation 2.286

SECONDARY outcome

Timeframe: Change from baseline for month 1

Population: ITT with LOCF

0 = Very loose (watery), 1 = Loose, 2 = Normal, 3 = Hard, 4 = Very hard (little balls)

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 1 Stool Consistency Change From Baseline	-0.51 Scale score Standard Deviation 0.690	-0.33 Scale score Standard Deviation 0.626

SECONDARY outcome

Timeframe: Change from baseline for month 1

Population: ITT with LOCF

0 = Absent,1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 1 Bowel Straining Change From Baseline	-0.53 Scale score Standard Deviation 0.739	-0.36 Scale score Standard Deviation 0.694

SECONDARY outcome

Timeframe: Change from baseline at 28 days

Population: ITT with LOCF

0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 1 Constipation Severity Change From Baseline	-0.41 Scale score Standard Deviation 0.602	-0.29 Scale score Standard Deviation 0.568

SECONDARY outcome

Timeframe: Change from baseline for month 1

Population: ITT with LOCF

Significantly worse = -3; Moderately worse = -2; A little bit worse = -1; Unchanged = 0; A little bit relieved=1; Moderately relieved=2; Significantly relieved = 3

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 1 Symptom Relief	0.66 Scale score Standard Deviation 1.212	0.57 Scale score Standard Deviation 1.088

SECONDARY outcome

Timeframe: Change from baseline at 12 weeks

Population: ITT without LOCF

Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire included 34 questions with 5 possible responses yielding the following sub-categories: dysphoria, interference with activity, body image, health worry, food avoidance, social reaction, sexual, and relationship Results range from 34 (low) to 100 (high); meaningful clinical improvement=14 point increase

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Quality of Life Change From Baseline	16.7 Scale score Standard Deviation 17.36	16.8 Scale score Standard Deviation 19.72

SECONDARY outcome

Timeframe: month 2 (28 days)

Population: ITT without LOCF

Monthly responder: >=Moderately relieved symptoms 4 weeks/month or Significantly relieved >= 2 weeks/month IF:

Rescue med use did not increase during the month; AND did not discontinue during the month for lack of efficacy; AND no Moderately worse or Significantly worse response in month.

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 2 Responder Rate	15.9 percent of participants	9.3 percent of participants

SECONDARY outcome

Timeframe: month 3 (28 days)

Population: ITT without LOCF

Symptoms >= Moderately relieved for 4 weeks/month or Significantly relieved for >=2 weeks/month AND:

1. Rescue medication use does not increase during the month as compared to baseline;

2. No discontinuation during the month due to lack of efficacy;AND

3. No ratings during the month of Moderately worse or Significantly worse.

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 3 Responder Rate	15.9 percent of participants	10.4 percent of participants

SECONDARY outcome

Timeframe: month 1 (28 days)

Population: ITT without LOCF

Symptoms >= Moderately relieved for 4 weeks/month or Significantly relieved for >=2 weeks/month AND:

1. Rescue medication use does not increase during the month as compared to baseline;

2. No discontinuation during the month due to lack of efficacy;AND

3. No ratings during the month of Moderately worse or Significantly worse.

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 1 Responder Rate	10.0 percent of participants	6.2 percent of participants

SECONDARY outcome

Timeframe: Change from baseline for month 2

Population: ITT with LOCF

0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 2 Abdominal Bloating Change From Baseline	-0.42 Scale score Standard Deviation 0.693	-0.35 Scale score Standard Deviation 0.621

SECONDARY outcome

Timeframe: Change from baseline for month 3

Population: ITT with LOCF

0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 3 Abdominal Bloating Change From Baseline	-0.43 Scale score Standard Deviation 0.734	-0.37 Scale score Standard Deviation 0.693

SECONDARY outcome

Timeframe: Change from baseline for month 2

Population: ITT with LOCF

Any bowel movement not associated with rescue medication use

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 2 Spontaneous Bowel Movement Frequency Rates Change From Baseline	1.59 SBM/week Standard Deviation 2.795	1.41 SBM/week Standard Deviation 2.587

SECONDARY outcome

Timeframe: Change from baseline for month 3

Population: ITT with LOCF

Any bowel movement not associated with rescue medication use

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 3 Spontaneous Bowel Movement Frequency Rates Change From Baseline	1.51 SBM/week Standard Deviation 2.990	1.39 SBM/week Standard Deviation 2.851

SECONDARY outcome

Timeframe: Change from baseline for month 2

Population: ITT with LOCF

0 = Very loose (watery), 1 = Loose, 2 = Normal, 3 = Hard, 4 = Very hard (little balls)

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 2 Stool Consistency Change From Baseline	-0.53 Scale score Standard Deviation 0.756	-0.38 Scale score Standard Deviation 0.658

SECONDARY outcome

Timeframe: Change from baseline for month 3

Population: ITT with LOCF

0 = Very loose (watery), 1 = Loose, 2 = Normal, 3 = Hard, 4 = Very hard (little balls)

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 3 Stool Consistency Change From Baseline	-0.52 Scale score Standard Deviation 0.725	-0.41 Scale score Standard Deviation 0.696

SECONDARY outcome

Timeframe: Change from baseline for month 2

Population: ITT with LOCF

0 = Absent,1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 2 Bowel Straining Change From Baseline	-0.58 Scale score Standard Deviation 0.846	-0.43 Scale score Standard Deviation 0.762

SECONDARY outcome

Timeframe: Change from baseline for month 3

0 = Absent,1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 3 Bowel Straining Change From Baseline	-0.56 Scale score Standard Deviation 0.847	-0.45 Scale score Standard Deviation 0.760

SECONDARY outcome

Timeframe: Change from baseline for month 2

Population: ITT with LOCF

0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 2 Constipation Severity Change From Baseline	-0.50 Scale score Standard Deviation 0.719	-0.40 Scale score Standard Deviation 0.670

SECONDARY outcome

Timeframe: Change from baseline for month 3

Population: ITT with LOCF

0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 3 Constipation Severity Change From Baseline	-0.51 Scale score Standard Deviation 0.755	-0.41 Scale score Standard Deviation 0.712

SECONDARY outcome

Timeframe: Change from baseline for month 2

Population: ITT with LOCF

Significantly worse = -3; Moderately worse = -2; A little bit worse = -1; Unchanged = 0; A little bit relieved=1; Moderately relieved=2; Significantly relieved = 3

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 2 Symptom Relief	0.76 Scale score Standard Deviation 1.278	0.59 Scale score Standard Deviation 1.203

SECONDARY outcome

Timeframe: Change from baseline for month 3

Population: ITT with LOCF

Significantly worse = -3; Moderately worse = -2; A little bit worse = -1; Unchanged = 0; A little bit relieved=1; Moderately relieved=2; Significantly relieved = 3

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 3 Symptom Relief	0.74 Scale score Standard Deviation 1.259	0.57 Scale score Standard Deviation 1.277

SECONDARY outcome

Timeframe: Change from baseline for month 1

Population: ITT with LOCF

0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 1 Abdominal Bloating Change From Baseline	-0.30 Scale score Standard Deviation 0.585	-0.24 Scale score Standard Deviation 0.516

SECONDARY outcome

Timeframe: Change from baseline for month 1

Population: ITT, with LOCF

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 1 Bowel Movement Frequency Rates Change From Baseline	1.22 BM/week Standard Deviation 2.234	0.88 BM/week Standard Deviation 2.093

SECONDARY outcome

Timeframe: Change from baseline for month 2

Population: ITT, with LOCF

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 2 Bowel Movement Frequency Rates Change From Baseline	1.23 BM/week Standard Deviation 2.440	1.10 BM/week Standard Deviation 2.581

SECONDARY outcome

Timeframe: Change from baseline for month 3

Population: ITT, with LOCF

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 3 Bowel Movement Frequency Rates Change From Baseline	1.15 BM/week Standard Deviation 2.744	1.04 BM/week Standard Deviation 2.731

SECONDARY outcome

Timeframe: Change from baseline for month 1

0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 1 Abdominal Pain Change From Baseline	-0.29 Scale Score Standard Deviation 0.588	-0.27 Scale Score Standard Deviation 0.508

SECONDARY outcome

Timeframe: Change from baseline for month 2

0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 2 Abdominal Pain Change From Baseline	-0.43 Scale Score Standard Deviation 0.695	-0.37 Scale Score Standard Deviation 0.614

SECONDARY outcome

Timeframe: Change from baseline for month 3

0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

Outcome measures

Measure	Lubiprostone Study Period I n=390 Participants Subjects who received active drug	Placebo Study Period I n=193 Participants Subjects who received placebo
Month 3 Abdominal Pain Change From Baseline	-0.42 Scale Score Standard Deviation 0.722	-0.36 Scale Score Standard Deviation 0.684

Adverse Events

Lubiprostone Study Period I

Serious events: 5 serious events

Other events: 75 other events

Deaths: 0 deaths

Placebo Study Period I

Serious events: 2 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Measure	Lubiprostone Study Period I n=396 participants at risk 8 mcg capsules twice daily (BID)	Placebo Study Period I n=192 participants at risk Matching placebo capsules twice daily (BID)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid gland cancer	0.25% 1/396 • Number of events 1 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population	0.00% 0/192 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.25% 1/396 • Number of events 1 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population	0.00% 0/192 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population
Cardiac disorders Mitral valve incompetence	0.25% 1/396 • Number of events 1 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population	0.00% 0/192 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population
Cardiac disorders Coronary artery disease	0.25% 1/396 • Number of events 1 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population	0.00% 0/192 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population
Cardiac disorders Cardiac arrest	0.25% 1/396 • Number of events 1 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population	0.00% 0/192 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population
Cardiac disorders Atrial fibrillation	0.25% 1/396 • Number of events 1 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population	0.00% 0/192 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population
Renal and urinary disorders Dysuria	0.25% 1/396 • Number of events 1 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population	0.00% 0/192 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/396 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population	0.52% 1/192 • Number of events 1 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population
Injury, poisoning and procedural complications Fall	0.00% 0/396 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population	0.52% 1/192 • Number of events 1 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population
Injury, poisoning and procedural complications Back injury	0.00% 0/396 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population	0.52% 1/192 • Number of events 1 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population

Other adverse events

Measure	Lubiprostone Study Period I n=396 participants at risk 8 mcg capsules twice daily (BID)	Placebo Study Period I n=192 participants at risk Matching placebo capsules twice daily (BID)
Gastrointestinal disorders Nausea	11.9% 47/396 • Number of events 47 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population	5.7% 11/192 • Number of events 11 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population
Gastrointestinal disorders Diarrhoea	7.1% 28/396 • Number of events 28 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population	5.7% 11/192 • Number of events 11 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population
Gastrointestinal disorders Abdominal Pain	5.6% 22/396 • Number of events 22 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population	6.2% 12/192 • Number of events 12 • Up to 12 weeks Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population

Additional Information

Medical Information Call Center

Mallinckrodt Pharmaceuticals

Phone: 800-556-3314

Email: clinicaltrials@mnk.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place