Trial Outcomes & Findings for Drug Interaction Study of Colchicine and Theophylline (NCT NCT01601132)
NCT ID: NCT01601132
Last Updated: 2013-06-17
Results Overview
The time to each the maximum or peak concentration of theophylline in the plasma, after a single dose on Day 1, and after a single dose on Day 19, following 14 days of colchicine dosing.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
30 participants
Primary outcome timeframe
Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration.
Results posted on
2013-06-17
Participant Flow
Participants took part in the study at one investigative site in the USA from 11 June 2012 to 01 July 2012.
Thirty non-smoking, adult male and female volunteers (ages 18 to 45 years) were enrolled in this single group study.
Participant milestones
| Measure |
Theophylline + Colchicine
Theophylline 300 mg, solution, orally, on Day 1, then colchicine 0.6 mg tablets, orally, twice daily on Days 5-18, then theophylline 300 mg, solution, orally together with colchicine 0.6 mg, tablet, orally on Day 19 followed by a last dose of colchicine 0.6 mg, tablet, orally, 12 hours later.
|
|---|---|
|
Overall Study
STARTED
|
30
|
|
Overall Study
COMPLETED
|
28
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Theophylline + Colchicine
Theophylline 300 mg, solution, orally, on Day 1, then colchicine 0.6 mg tablets, orally, twice daily on Days 5-18, then theophylline 300 mg, solution, orally together with colchicine 0.6 mg, tablet, orally on Day 19 followed by a last dose of colchicine 0.6 mg, tablet, orally, 12 hours later.
|
|---|---|
|
Overall Study
Patient withdrew consent
|
1
|
|
Overall Study
Protocol deviation
|
1
|
Baseline Characteristics
Drug Interaction Study of Colchicine and Theophylline
Baseline characteristics by cohort
| Measure |
Theophylline + Colchicine
n=30 Participants
Theophylline 300 mg, solution, orally, on Day 1, then colchicine 0.6 mg tablets, orally, twice daily on Days 5-18, then theophylline 300 mg, solution, orally together with colchicine 0.6 mg, tablet, orally on Day 19 followed by a last dose of colchicine 0.6 mg, tablet, orally, 12 hours later.
|
|---|---|
|
Age Continuous
|
31.8 Years
STANDARD_DEVIATION 7.8 • n=99 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
1 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
4 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
White
|
25 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
23 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
7 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
30 Participants
n=99 Participants
|
|
Tobacco history
Never used tobacco
|
26 Participants
n=99 Participants
|
|
Tobacco history
Past smoker or has used other forms of tobacco
|
4 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration.Population: The pharmacokinetic (PK) population is defined as any participant who took a single dose of study medication and had sufficient blood sampling to characterize the non-compartmental PK parameters. Patients with available data are included in the analysis.
The time to each the maximum or peak concentration of theophylline in the plasma, after a single dose on Day 1, and after a single dose on Day 19, following 14 days of colchicine dosing.
Outcome measures
| Measure |
Theophylline
n=30 Participants
Theophylline 300 mg, solution, orally, on Day 1.
|
Theophylline + Colchicine
n=28 Participants
Theophylline 300 mg, solution, orally together with colchicine 0.6 mg, tablet, orally on Day 19 followed by a last dose of colchicine 0.6 mg, tablet, orally, 12 hours later.
|
|---|---|---|
|
Time to Reach the Maximum Plasma Concentration (Tmax) of Theophylline
|
1.25 hours
Interval 0.25 to 4.0
|
1.5 hours
Interval 0.25 to 4.0
|
PRIMARY outcome
Timeframe: Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration.Population: The pharmacokinetic (PK) population is defined as any participant who took a single dose of study medication and had sufficient blood sampling to characterize the non-compartmental PK parameters.
The maximum or peak concentration of theophylline in the plasma, after a single dose on Day 1, and after another single dose on Day 19 following 14 days of colchicine dosing.
Outcome measures
| Measure |
Theophylline
n=30 Participants
Theophylline 300 mg, solution, orally, on Day 1.
|
Theophylline + Colchicine
n=28 Participants
Theophylline 300 mg, solution, orally together with colchicine 0.6 mg, tablet, orally on Day 19 followed by a last dose of colchicine 0.6 mg, tablet, orally, 12 hours later.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Theophylline
|
11.0 μg/mL
Standard Deviation 2.16
|
11.7 μg/mL
Standard Deviation 2.79
|
PRIMARY outcome
Timeframe: Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration.Population: PK population
The area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration (t), as calculated by the linear trapezoidal rule for theophylline.
Outcome measures
| Measure |
Theophylline
n=30 Participants
Theophylline 300 mg, solution, orally, on Day 1.
|
Theophylline + Colchicine
n=28 Participants
Theophylline 300 mg, solution, orally together with colchicine 0.6 mg, tablet, orally on Day 19 followed by a last dose of colchicine 0.6 mg, tablet, orally, 12 hours later.
|
|---|---|---|
|
Area Under the Concentration Versus Time Curve From Time 0 to Time of the Last Quantifiable Concentration[AUC(0-t)]
|
155.6 hours*μg/mL
Standard Deviation 34.86
|
164.0 hours*μg/mL
Standard Deviation 40.01
|
PRIMARY outcome
Timeframe: Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration.Population: PK population
The area under the plasma concentration versus time curve from time 0 to infinity. \[AUC(0-∞)\] was calculated as the sum of AUC (0-t) plus the ratio of the last measurable plasma concentration to the elimination rate constant for theophylline.
Outcome measures
| Measure |
Theophylline
n=30 Participants
Theophylline 300 mg, solution, orally, on Day 1.
|
Theophylline + Colchicine
n=28 Participants
Theophylline 300 mg, solution, orally together with colchicine 0.6 mg, tablet, orally on Day 19 followed by a last dose of colchicine 0.6 mg, tablet, orally, 12 hours later.
|
|---|---|---|
|
Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]
|
180.7 hours*μg/mL
Standard Deviation 62.30
|
185.7 hours*μg/mL
Standard Deviation 54.46
|
PRIMARY outcome
Timeframe: Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration.Population: PK population
Apparent total body clearance after oral administration, calculated as Dose /(AUC0-∞).
Outcome measures
| Measure |
Theophylline
n=30 Participants
Theophylline 300 mg, solution, orally, on Day 1.
|
Theophylline + Colchicine
n=28 Participants
Theophylline 300 mg, solution, orally together with colchicine 0.6 mg, tablet, orally on Day 19 followed by a last dose of colchicine 0.6 mg, tablet, orally, 12 hours later.
|
|---|---|---|
|
Apparent Total Body Clearance (CL/F) of Theophylline
|
1.832 liters/hour
Standard Deviation 0.5849
|
1.741 liters/hour
Standard Deviation 0.4799
|
PRIMARY outcome
Timeframe: Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration.Population: PK population
Apparent total volume of distribution after oral administration, calculated as Dose /(AUC0-∞) \* Apparent first-order elimination rate constant \[Kel\])
Outcome measures
| Measure |
Theophylline
n=30 Participants
Theophylline 300 mg, solution, orally, on Day 1.
|
Theophylline + Colchicine
n=28 Participants
Theophylline 300 mg, solution, orally together with colchicine 0.6 mg, tablet, orally on Day 19 followed by a last dose of colchicine 0.6 mg, tablet, orally, 12 hours later.
|
|---|---|---|
|
Apparent Total Volume of Distribution (Vd/F) of Theophylline
|
36.21 liters
Standard Deviation 13.03
|
34.44 liters
Standard Deviation 10.39
|
Adverse Events
Theophylline
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Colchicine
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Colchicine + Theophylline
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Theophylline
n=30 participants at risk
Theophylline 300 mg, solution, orally, on Day 1, followed by a 4-day washout period.
|
Colchicine
n=30 participants at risk
Colchicine, 0.6 mg tablet, orally, twice daily, from Days 5-18.
|
Colchicine + Theophylline
n=29 participants at risk
Theophylline 300 mg, solution, orally, single dose and colchicine 0.6 mg, tablets, orally, twice daily, on Day 19.
|
|---|---|---|---|
|
Cardiac disorders
Palpitations
|
3.3%
1/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
6.9%
2/29 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Cardiac disorders
Tachycardia
|
3.3%
1/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/29 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Abdominal pain
|
6.7%
2/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
16.7%
5/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
17.2%
5/29 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Diarrhoea
|
3.3%
1/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
26.7%
8/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
6.9%
2/29 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
3.3%
1/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/29 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
6.9%
2/29 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Nausea
|
16.7%
5/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
13.8%
4/29 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
6.7%
2/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
3.4%
1/29 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
General disorders
Feeling jittery
|
3.3%
1/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
6.7%
2/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
3.4%
1/29 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
3.3%
1/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/29 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
3.3%
1/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/29 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Nervous system disorders
Dizziness
|
3.3%
1/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
3.3%
1/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
17.2%
5/29 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Nervous system disorders
Headache
|
6.7%
2/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
3.3%
1/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
13.8%
4/29 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Nervous system disorders
Somnolence
|
6.7%
2/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
3.4%
1/29 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
3.3%
1/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/29 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
3.3%
1/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/30 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/29 • From the time of first study drug administration until 5 days after last dose.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
Additional Information
Sr. VP, Clinical Science
Takeda Global Research and Development Center, Inc.
Phone: 800-778-2860
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
- Publication restrictions are in place
Restriction type: OTHER