Oxycodone DETERx™ Versus Placebo in Chronic Low Back Pain (CLBP)

• Sponsor: Collegium Pharmaceutical, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01685684
• Collaborator: (none)
• Enrollment: 740
• Locations: 45
• Arms: 2
• Duration (Months): 23
• Patients Per Site: 16.4
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the analgesic efficacy of Oxycodone DETERx compared with placebo in opioid-experienced and opioid-naive subjects with moderate-to-severe chronic low back pain requiring around-the-clock opioid analgesia for an extended period of time.

Condition or Disease	Intervention/Treatment	Phase
Chronic Low Back Pain	Drug: Oxycodone DETERx; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 740 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multi-Center, Randomized, Double-blind, Placebo-Controlled, Safety, Tolerability, and Efficacy Study of Oxycodone DETERx™ Versus Placebo in Opioid-Experienced and Opioid-Naive Subjects With Moderate-to-Severe Chronic Low Back Pain
• Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jul 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oxycodone DETERx	Drug: Oxycodone DETERx; 40-160 mg total daily dose of oxycodone DETERx, divided into 2 doses, q12h
Placebo Comparator: Placebo	Drug: Placebo; Placebo, divided into 2 doses, q12h

Outcome Measures

Primary Outcome Measures

1. Change in Average Pain Intensity Measured by the Change in Pain Intensity-Numeric Rating Scale (PI-NRS) Scores From Randomization Baseline to Week 12 of the Double-blind Maintenance Phase [Randomized Baseline through Week 12]

   The PI-NRS is an 11-point numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain).

Secondary Outcome Measures

1. Time-to-exit From the Study for All Causes [Randomization Baseline through Week 12]

   Survival analysis. Measure type indicated as 'Number' below represents 25% quartile, given that the median was not reached. These data are consistent with subject completion in the Participant Flow module.

2. Percent Reduction in Pain Intensity for Responders [Screening Baseline through Week 12]

   Includes the cumulative distribution of subjects with an improvement in pain intensity, as measured on an 11-point PI-NRS scale, and the proportion of responders with at least 30% and at least 50% reduction in pain intensity.

3. Weekly Changes in Pain Intensity [Randomization Baseline and weekly through Week 12]

   Weekly pain intensity scores were calculated based on averaged daily pain intensity scores (PI-NRS). Increases to the weekly change in pain intensity, correspond to increases in the PI-NRS scores (i.e. more pain).

4. Rescue Medication Usage by Dose [Randomization Baseline through Week 12]

   Evaluation of the total amount of rescue medication used (number of doses per day, number of doses per week, and total number of doses while on-study)

5. Rescue Medication Use by Dosage [Randomization Baseline through Week 12]

   Evaluation of the total amount of rescue medication used (by milligrams of dosage per day, dosage per week, and total dosage while on-study)

6. Patient Global Impression of Change (PGIC) [Screening Baseline through Week 12]

   The PGIC scale is a self-reported assessment that assesses a subject's impression of his/her change in activity limitations, symptoms, emotions, and the overall quality of life as they relate to his/her painful condition. The 7-point PGIC assessment includes "very much improved", "improved", "a little improved", "no change", "a little worse", "worse", and "very much worse".

7. Changes in Quality of Life [Randomization Baseline through Week 12]

   Short Form 12 Question Health Survey version 2 (SF-12v2) is a self-report survey designed to measure general quality of life from the subject's point of view. The survey includes eight domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. Physical (PCS) and mental component scores (MCS) are also calculated. Positive values indicate improvement from randomization baseline to Week 12.

8. Change in Level of Physical Disability Using the Roland Morris Disability Questionnaire (RMDQ) [Randomization Baseline and Week 12]

   The Roland Morris Disability Questionnaire (RMDQ) is a self-administered questionnaire designed to assess physical disability caused by lower back pain. The RMDQ contains 24 sentences that subjects used to describe themselves when they have back pain. The RMDQ score is the total number of items checked which is from a minimum of 0 to a maximum of 24; the greater the score the grater the physical disability due to lower back pain.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or non-pregnant female 18-75 years of age (inclusive) at the time of consent.

• Must have a clinical diagnosis of moderate-to-severe CLBP for a minimum of 6 months prior to screening.

• Must qualify for ATC opioid therapy for treatment of CLBP.

• Must be classified as non-malignant and non-neuropathic (Class 1 and 2), neuropathic (Class 3), or symptomatic for more than 6 months after low back pain surgery (Class 9) based on the Quebec Task Force Scale score.

• Female subjects of childbearing potential will use an acceptable method of birth control.

• Must be in general good health based on screening physical examination.

• Must be willing and able to comply with all study procedures and visit requirements.

Exclusion Criteria:

• Known to be refractory or intolerant to the analgesic effects of opioids or have failed previous opioid therapy.

• A medical condition that would compromise the subject's ability to swallow, absorb, metabolize, or excrete the study drug, including (but not limited to) intractable nausea and/or vomiting and/or severe gastrointestinal narrowing (pathologic or iatrogenic), bowel obstruction, ileostomy, colostomy, or is suspected of having paralytic ileus.

• A surgical procedure for back pain within 6 months prior to the Screening Visit.

• Any other chronic pain condition other than CLBP that would interfere with the assessment of CLBP (e.g., osteoarthritis, rheumatoid arthritis, post-herpetic neuralgia, pain associated with diabetic neuropathy, fibromyalgia, migraine headaches requiring opioid therapy).

• Known history of major depressive disorder that is not controlled with medication or has other conditions that produce significant cognitive or emotional disability.

• Any clinically significant unstable medical abnormality or acute or chronic disease of the cardiovascular, gastrointestinal, respiratory (e.g., chronic obstructive pulmonary disease), hepatic, or renal systems.

• Known history of alcohol and/or drug abuse.

• Positive urine drug screen for illegal or non-prescribed drugs

• Known history of seizure disorder, epilepsy, convulsions, or increased intracranial pressure anytime during the subject's life except pediatric febrile seizures.

• Known history of head injury within 6 months of Screening Visit.

• Current malignancy or a history within past 2 years of malignancy, with the exception of basal cell carcinoma or cervical carcinoma in situ that have been successfully treated.

• Positive for human immunodeficiency virus (HIV) or hepatitis B surface antigen, or hepatitis C antibody

• Subject is not able or is unwilling to meet the study attendance requirements.

Other protocol specific inclusion and exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Mesa	Arizona	United States	85282
2		Phoenix	Arizona	United States	85050
3		Tucson	Arizona	United States	85704
4		Anaheim	California	United States	92801
5		Anaheim	California	United States	92804
6		Buena Park	California	United States	90620
7		Cerritos	California	United States	90703
8		Escondido	California	United States	92025
9		La Mesa	California	United States	91942
10		Napa	California	United States	94558
11		Pasadena	California	United States	91105
12		DeLand	Florida	United States	32720
13		Naples	Florida	United States	34108
14		Orlando	Florida	United States	32860
15		Plantation	Florida	United States	33317
16		West Palm Beach	Florida	United States	33409
17		Columbus	Georgia	United States	31904
18		Marietta	Georgia	United States	30060
19		Indianapolis	Indiana	United States	46203
20		Valparaiso	Indiana	United States	46383
21		Overland Park	Kansas	United States	66211
22		Brockton	Massachusetts	United States	02301
23		Natick	Massachusetts	United States	01760
24		Watertown	Massachusetts	United States	02472
25		Pascagoula	Mississippi	United States	39581
26		Saint Louis	Missouri	United States	63128
27		Las Vegas	Nevada	United States	89123
28		Berlin	New Jersey	United States	08009
29		New York	New York	United States	10128
30		Rochester	New York	United States	14618
31		Williamsville	New York	United States	14221
32		Winston-Salem	North Carolina	United States	27103
33		Cincinnati	Ohio	United States	45242
34		Oklahoma City	Oklahoma	United States	73116
35		Philadelphia	Pennsylvania	United States	19139
36		Charleston	South Carolina	United States	29406
37		Rapid City	South Dakota	United States	57702
38		New Tazewell	Tennessee	United States	37825
39		Austin	Texas	United States	78731
40		Dallas	Texas	United States	75230
41		Houston	Texas	United States	77098
42		Orem	Utah	United States	84058
43		Salt Lake City	Utah	United States	84106
44		Roanoke	Virginia	United States	24018
45		Bellevue	Washington	United States	98007

Sponsors and Collaborators

• Collegium Pharmaceutical, Inc.

Investigators

• Study Director: Richard Malamut, MD, Collegium Pharmaceutical, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Collegium Pharmaceutical, Inc.
• ClinicalTrials.gov Identifier: NCT01685684
• Other Study ID Numbers: CP-OXYDET-08
• First Posted: Sep 14, 2012
• Last Update Posted: Oct 19, 2020
• Last Verified: Feb 1, 2019

• Keywords provided by Collegium Pharmaceutical, Inc.: Low back pain; Chronic back pain; Back pain; Opioid; Oxycodone; DETERx; Chronic pain; Chronic low back pain; CLBP; Xtampza
• Additional relevant MeSH terms: Back Pain; Low Back Pain; Oxycodone

Study Results

Participant Flow

Pre-assignment Detail	The titration (i.e., enrichment) phase of the study was designed to titrate patients to a dose of Oxycodone DETERx that balanced pain control and tolerability to ensure that only patients who experienced a substantial reduction from the screening pain assessment and who can tolerate side effects continue into the Double-blind Maintenance Phase.

Arm/Group Title	Oxycodone DETERx (Titration Phase)	Oxycodone DETERx (Double-blind Maintenance Phase)	Placebo (Double-blind Maintenance Phase)
Arm/Group Description	Achieve a stable Oxycodone DETERx dose of 40-160 mg total daily dose.	Oxycodone DETERx: 40-160 mg total daily dose of oxycodone DETERx, divided into 2 doses, q12h	Placebo: Placebo, divided into 2 doses, q12h
Period Title: Titration Phase
STARTED	740	0	0
COMPLETED	389	0	0
NOT COMPLETED	351	0	0
Period Title: Titration Phase
STARTED	0	193	196
COMPLETED	0	122	100
NOT COMPLETED	0	71	96

Baseline Characteristics

Arm/Group Title	Oxycodone DETERx (Double-blind Maintenance Phase)	Placebo (Double-blind Maintenance Phase)	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	193	196	389
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.2 (13.31)	49.9 (12.56)	49.5 (12.93)
Sex: Female, Male (Count of Participants)
Female	103 53.4%	103 52.6%	206 53%
Male	90 46.6%	93 47.4%	183 47%
Pain Intensity-Numeric Rating Scale (PI-NRS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	3.0 (1.04)	2.9 (0.97)	2.9 (1.00)

Outcome Measures

1. Primary Outcome

Title	Change in Average Pain Intensity Measured by the Change in Pain Intensity-Numeric Rating Scale (PI-NRS) Scores From Randomization Baseline to Week 12 of the Double-blind Maintenance Phase
Description	The PI-NRS is an 11-point numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain).
Time Frame	Randomized Baseline through Week 12

Outcome Measure Data

Analysis Population Description

One subject is missing all Average Weekly Pain Scores after Screening in the Oxycodone DETERx treatment group. This subject has been excluded from the analysis.

Arm/Group Title	Oxycodone DETERx (Double-blind Maintenance Phase)	Placebo (Double-blind Maintenance Phase)
Arm/Group Description
Measure Participants	192	196
Mean (Standard Error) [units on a scale]	0.29 (0.146)	1.85 (0.223)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oxycodone DETERx (Double-blind Maintenance Phase), Placebo (Double-blind Maintenance Phase)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	z-test
	Comments
Method of Estimation	Estimation Parameter	Marginal Mean Difference (Net)
	Estimated Value	-1.56
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.267
	Estimation Comments

2. Secondary Outcome

Title	Time-to-exit From the Study for All Causes
Description	Survival analysis. Measure type indicated as 'Number' below represents 25% quartile, given that the median was not reached. These data are consistent with subject completion in the Participant Flow module.
Time Frame	Randomization Baseline through Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxycodone DETERx (Double-blind Maintenance Phase)	Placebo (Double-blind Maintenance Phase)
Arm/Group Description
Measure Participants	193	196
Number (95% Confidence Interval) [Days]	58.0	35.0

3. Secondary Outcome

Title	Percent Reduction in Pain Intensity for Responders
Description	Includes the cumulative distribution of subjects with an improvement in pain intensity, as measured on an 11-point PI-NRS scale, and the proportion of responders with at least 30% and at least 50% reduction in pain intensity.
Time Frame	Screening Baseline through Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxycodone DETERx (Double-blind Maintenance Phase)	Placebo (Double-blind Maintenance Phase)
Arm/Group Description
Measure Participants	193	196
Subjects with 30% Improvement	95 49.2%	65 33.2%
Subjects with 50% Improvement	74 38.3%	48 24.5%

4. Secondary Outcome

Title	Weekly Changes in Pain Intensity
Description	Weekly pain intensity scores were calculated based on averaged daily pain intensity scores (PI-NRS). Increases to the weekly change in pain intensity, correspond to increases in the PI-NRS scores (i.e. more pain).
Time Frame	Randomization Baseline and weekly through Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxycodone DETERx (Double-blind Maintenance Phase)	Placebo (Double-blind Maintenance Phase)
Arm/Group Description
Measure Participants	193	196
Week 1	0.1 (0.85)	0.3 (1.17)
Week 2	0.0 (1.05)	0.4 (1.46)
Week 3	0.1 (1.14)	0.5 (1.78)
Week 4	0.1 (1.25)	0.8 (1.86)
Week 5	0.2 (1.41)	0.7 (1.86)
Week 6	0.2 (1.45)	0.7 (1.95)
Week 7	0.1 (1.35)	0.7 (2.00)
Week 8	0.0 (1.29)	0.8 (2.06)
Week 9	0.1 (1.59)	0.7 (2.15)
Week 10	0.2 (1.55)	0.7 (2.20)
Week 11	0.2 (1.62)	0.8 (2.23)
Week 12	0.3 (1.54)	0.8 (2.29)

5. Secondary Outcome

Title	Rescue Medication Usage by Dose
Description	Evaluation of the total amount of rescue medication used (number of doses per day, number of doses per week, and total number of doses while on-study)
Time Frame	Randomization Baseline through Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxycodone DETERx (Double-blind Maintenance Phase)	Placebo (Double-blind Maintenance Phase)
Arm/Group Description
Measure Participants	193	196
Doses per Day	0.15 (0.297)	0.23 (0.458)
Doses per Week	1.04 (2.081)	1.60 (3.206)
Total Number of Doses	8.0 (16.38)	11.2 (31.55)

6. Secondary Outcome

Title	Rescue Medication Use by Dosage
Description	Evaluation of the total amount of rescue medication used (by milligrams of dosage per day, dosage per week, and total dosage while on-study)
Time Frame	Randomization Baseline through Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxycodone DETERx (Double-blind Maintenance Phase)	Placebo (Double-blind Maintenance Phase)
Arm/Group Description
Measure Participants	193	196
Dosage per Day	144.63 (289.472)	189.32 (317.605)
Dosage per Week	1012.39 (2026.298)	1325.27 (2223.231)
Total Dosage	7873.1 (16665.70)	9028.1 (20441.67)

7. Secondary Outcome

Title	Patient Global Impression of Change (PGIC)
Description	The PGIC scale is a self-reported assessment that assesses a subject's impression of his/her change in activity limitations, symptoms, emotions, and the overall quality of life as they relate to his/her painful condition. The 7-point PGIC assessment includes "very much improved", "improved", "a little improved", "no change", "a little worse", "worse", and "very much worse".
Time Frame	Screening Baseline through Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxycodone DETERx (Double-blind Maintenance Phase)	Placebo (Double-blind Maintenance Phase)
Arm/Group Description
Measure Participants	122	100
Very Much Improved	36 18.7%	17 8.7%
Improved	52 26.9%	39 19.9%
A Little Improved	23 11.9%	26 13.3%
No Change	9 4.7%	12 6.1%
A Little Worse	0 0%	4 2%
Worse	2 1%	1 0.5%
Very Much Worse	0 0%	1 0.5%

8. Secondary Outcome

Title	Changes in Quality of Life
Description	Short Form 12 Question Health Survey version 2 (SF-12v2) is a self-report survey designed to measure general quality of life from the subject's point of view. The survey includes eight domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. Physical (PCS) and mental component scores (MCS) are also calculated. Positive values indicate improvement from randomization baseline to Week 12.
Time Frame	Randomization Baseline through Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxycodone DETERx (Double-blind Maintenance Phase)	Placebo (Double-blind Maintenance Phase)
Arm/Group Description
Measure Participants	193	196
Physical Component Score	7.524 (10.1327)	3.622 (9.4290)
Mental Component Score	-2.554 (10.4145)	0.674 (11.1676)
Physical Functioning	0.6 (1.35)	0.5 (1.00)
Role Physical	1.2 (2.35)	0.6 (2.16)
Bodily Pain	0.7 (1.16)	0.4 (1.29)
General Health	0.28 (0.784)	0.22 (0.789)

9. Secondary Outcome

Title	Change in Level of Physical Disability Using the Roland Morris Disability Questionnaire (RMDQ)
Description	The Roland Morris Disability Questionnaire (RMDQ) is a self-administered questionnaire designed to assess physical disability caused by lower back pain. The RMDQ contains 24 sentences that subjects used to describe themselves when they have back pain. The RMDQ score is the total number of items checked which is from a minimum of 0 to a maximum of 24; the greater the score the grater the physical disability due to lower back pain.
Time Frame	Randomization Baseline and Week 12

Outcome Measure Data

Analysis Population Description

The RMDQ was analyzed and presented as a change from Randomization Baseline to Week 12. Subjects' scores from Early Discontinuation visits were not included in this analysis.

Arm/Group Title	Oxycodone DETERx (Double-blind Maintenance Phase)	Placebo (Double-blind Maintenance Phase)
Arm/Group Description
Measure Participants	109	90
Mean (Standard Deviation) [units on a scale]	0.4 (4.83)	0.7 (5.32)

Adverse Events

Time Frame	Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first.
Adverse Event Reporting Description	Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.
Arm/Group Title	Screening		Oxycodone DETERx (Titration Phase)		Oxycodone DETERx (Double-blind Maintenance Phase)		Placebo (Double-blind Maintenance Phase)
Arm/Group Description	Serious Adverse Event (SAE) collection started during screening.
All Cause Mortality
	Screening		Oxycodone DETERx (Titration Phase)		Oxycodone DETERx (Double-blind Maintenance Phase)		Placebo (Double-blind Maintenance Phase)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Screening		Oxycodone DETERx (Titration Phase)		Oxycodone DETERx (Double-blind Maintenance Phase)		Placebo (Double-blind Maintenance Phase)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/1297 (0.2%)		8/740 (1.1%)		2/193 (1%)		2/196 (1%)
Cardiac disorders
Sinus Bradycardia	1/1297 (0.1%)		0/740 (0%)		0/193 (0%)		0/196 (0%)
Angina unstable	0/1297 (0%)		1/740 (0.1%)		0/193 (0%)		0/196 (0%)
Gastrointestinal disorders
Colitis ischaemic	0/1297 (0%)		1/740 (0.1%)		0/193 (0%)		0/196 (0%)
Gastrooesophageal reflux disease	0/1297 (0%)		1/740 (0.1%)		0/193 (0%)		0/196 (0%)
General disorders
Sudden cardiac death	0/1297 (0%)		1/740 (0.1%)		0/193 (0%)		0/196 (0%)
Non-cardiac chest pain	0/1297 (0%)		0/740 (0%)		0/193 (0%)		1/196 (0.5%)
Infections and infestations
Pneumonia	0/1297 (0%)		1/740 (0.1%)		0/193 (0%)		0/196 (0%)
Atypical pneumonia	0/1297 (0%)		0/740 (0%)		1/193 (0.5%)		0/196 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pituitary tumour benign	0/1297 (0%)		1/740 (0.1%)		0/193 (0%)		0/196 (0%)
Benign hydatidiform mole	0/1297 (0%)		0/740 (0%)		0/193 (0%)		1/196 (0.5%)
Psychiatric disorders
Suicidal ideation	0/1297 (0%)		1/740 (0.1%)		0/193 (0%)		0/196 (0%)
Respiratory, thoracic and mediastinal disorders
Emphysema	1/1297 (0.1%)		0/740 (0%)		0/193 (0%)		0/196 (0%)
Asthma	0/1297 (0%)		1/740 (0.1%)		1/193 (0.5%)		0/196 (0%)
Other (Not Including Serious) Adverse Events
	Screening		Oxycodone DETERx (Titration Phase)		Oxycodone DETERx (Double-blind Maintenance Phase)		Placebo (Double-blind Maintenance Phase)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		531/740 (71.8%)		60/193 (31.1%)		39/196 (19.9%)
Gastrointestinal disorders
Nausea	0/0 (NaN)		123/740 (16.6%)		21/193 (10.9%)		9/196 (4.6%)
Constipation	0/0 (NaN)		96/740 (13%)		10/193 (5.2%)		1/196 (0.5%)
Vomiting	0/0 (NaN)		47/740 (6.4%)		8/193 (4.1%)		3/196 (1.5%)
Nervous system disorders
Headache	0/0 (NaN)		103/740 (13.9%)		12/193 (6.2%)		23/196 (11.7%)
Somnolence	0/0 (NaN)		65/740 (8.8%)		1/193 (0.5%)		0/196 (0%)
Dizziness	0/0 (NaN)		42/740 (5.7%)		3/193 (1.6%)		0/196 (0%)
Skin and subcutaneous tissue disorders
Pruritus	0/0 (NaN)		55/740 (7.4%)		5/193 (2.6%)		3/196 (1.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If a joint manuscript has not been submitted for publication within twelve (12) months of completion or termination of the study, the PI is free to publish separately, upon provision of any proposed publication or manuscript to the Sponsor at least sixty (60) days before it is submitted or otherwise disclosed.