Study of COV795 in Subjects With Osteoarthritis or Chronic Low Back Pain

• Sponsor: Mallinckrodt (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01451385
• Collaborator: (none)
• Enrollment: 376
• Locations: 42
• Arm: 1
• Duration (Months): 8.9
• Patients Per Site: 9
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The primary objective is to demonstrate the safety and tolerability of COV795 with up to 35 days use as evaluated by physical exam, vital signs, pulse oximetry, clinical laboratory tests, and other adverse events (AEs).

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis; Low Back Pain	Drug: COV795	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 376 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Safety Study of COV795 in Subjects With Osteoarthritis or Chronic Low Back Pain
• Study Start Date: Sep 20, 2011
• Actual Primary Completion Date: Jun 18, 2012
• Actual Study Completion Date: Jun 18, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: COV795 Participants receive 2 tablets of COV795 every 12 hours for up to 35 days	Drug: COV795; COV795 is a multilayer extended-release tablet for oral administration of oxycodone hydrochloride (15 mg) and acetaminophen (650 mg); Other Names: MNK795

Outcome Measures

Primary Outcome Measures

1. Summary of Adverse Events (AEs) [5 Weeks]

   Collection of AEs began with subject's signing of the informed consent form, continued throughout the trial, and ended 7 days following the last dose of study drug, or at early termination. Treatment emergent AEs (TEAEs) are AEs that occurred after the first dose of study drug. TEAEs leading to discontinuation include 2 subjects who died (deaths not related to study drug). Clinically significant changes in values from physical exam, vital signs, clinical laboratory tests, and pulse oximetry were included as treatment emergent adverse events (TEAEs).

Secondary Outcome Measures

1. Modified Brief Pain Index - Short Form: Pain Intensity [at end of treatment (within 5 weeks)]

   Participants rate their pain on a score from 0=no pain to 10=pain as bad as you can imagine

2. Modified Brief Pain Index - Short Form: Percent Pain Relief From Medication [at end of treatment (within 5 weeks)]

   Participants rate percent pain relief from medication on a scale from 0% (no relief) to 100% (complete relief)

3. Modified Brief Pain Inventory-Short Form: Pain Interference Scores [at end of treatment (within 5 weeks)]

   Participants answer several questions about how much the pain interferes with their quality of life. The answers range from 0 = no interference to 10=completely interferes, and the average score for all the questions is recorded.

4. Western Ontario and McMaster Universities Arthritis Index (WOMAC) Questionnaire for Participants With Osteoarthritis (OA) of the Hip or Knee: Pain Score [End of treatment (within 5 weeks)]

   Disease-specific quality of life is assessed using the WOMAC questionnaire (48-hour version) for participants with osteoarthritis (OA) of the hip or knee. The WOMAC pain score ranges from 0 to 20, with higher scores representing worse pain.

5. WOMAC Questionnaire for Participants With Osteoarthritis (OA) of the Hip or Knee: Stiffness Score [End of treatment (within 5 weeks)]

   Disease-specific quality of life is assessed using the WOMAC questionnaire (48-hour version) for participants with osteoarthritis (OA) of the hip or knee. The WOMAC stiffness score ranges from 0 to 8, with higher scores representing worse stiffness.

6. WOMAC Questionnaire for Participants With Osteoarthritis (OA) of the Hip or Knee: Physical Function Score [End of treatment (within 5 weeks)]

   Disease-specific quality of life is assessed using the WOMAC questionnaire (48-hour version) for participants with osteoarthritis (OA) of the hip or knee. The WOMAC physical function score ranges from 0 to 68, with higher scores representing worse functional limitations.

7. WOMAC Questionnaire for Participants With Osteoarthritis (OA) of the Hip or Knee: Total Score [End of treatment (within 5 weeks)]

   Disease-specific quality of life is assessed using the WOMAC questionnaire (48-hour version) for participants with osteoarthritis (OA) of the hip or knee. The WOMAC total score ranges from 0 to 96, with higher scores representing worse pain/disability.

8. Roland-Morris Low Back Pain and Disability Scores for Participants With Chronic Low Back Pain [End of treatment (within 5 weeks)]

   Roland-Morris Low Back Pain and Disability Scores for participants with chronic low back pain range from 0 to 24, with higher scores representing greater disability.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion

1. Be considered in general good health based upon medical and surgical history, vital signs, pulse oximetry, physical exam, clinical lab tests, and electrocardiogram (ECG).

2. Be ≥18 years of age

3. Female subjects are eligible if not pregnant, not lactating or not planning to become pregnant within the next 2 months; surgically sterile or at least 2 years postmenopausal, or practicing an acceptable form of birth control for the duration of the study

4. Male subjects biologically capable of having children must agree to the use of a reliable method of birth control for the duration of the study

5. Have a clinical diagnosis of one of the following:

• Osteoarthritis (OA) of the knee or hip for at least one year based on the American College of Rheumatology (ACR) criteria

• Moderate to severe chronic lower back pain (CLBP), i.e. pain that occurs in an area with boundaries between the lowest rib and the crease of the buttocks that

1. must have been present for at least several hours a day for a minimum of 3 months, 2) is not due to a known malignancy, and 3) must be classified as non-neuropathic, neuropathic, or symptomatic for more than 6 months after lower back pain (LBP) surgery based on the Quebec Task Force Classification of Spinal Disorders

1. Have an average in-clinic pain score of ≥3 on the 11-point (0-10) numerical rating scale (NRS) as an average for the last 24 hours at screening visit.

2. Have a pain intensity score of ≥4 on NRS as an average for the last 24 hours at baseline visit.

3. Must, in the investigator's opinion, qualify for opioid therapy for their CLBP or OA.

4. Voluntarily provide written informed consent.

Exclusion

1. Have any clinically significant condition or unstable inter-current illness that would preclude study participation or interfere with the assessment of pain and other symptoms of CLBP or OA or would increase the risk of opioid-related AEs

2. Have an uncontrolled or poorly controlled major psychiatric condition, or have clinically significant anxiety or depression

3. Have an active malignancy or history of malignancy within 2 years

4. Have a history of seizures (except pediatric febrile seizures) or cognitive dysfunction

5. Have clinically significant ECG abnormalities or have uncontrolled hypo- or hypertension

6. Had arthroscopic or open surgery on either knee or hip selected as the primary OA study joint within 6 months

7. For CLBP, had a surgical procedure for back pain within 6 months

8. For CLBP participants, had a nerve or plexus block within 1 month or botulinum toxin injection in the lower back region within 3 months. For participants with OA of the selected primary joint, had joint injection within 1 month prior to Screening Visit 1.

9. Had surgical implants of either the knee or hip selected as the primary OA joint

10. Had gastric reduction surgery

11. Have been taking opioids in equivalents to more than 20 mg oxycodone hydrochloride (OC) or more than 40 mg morphine sulfate (MS) orally per day, or have been taking opioid medications 4 times a week or more

12. Unable to discontinue use of prohibited medications

13. Have a known allergy or hypersensitivity to opioids, OC, acetaminophen (APAP) or ibuprofen.

14. Have abnormal clinical laboratory tests at screening

15. Have a history of substance or alcohol abuse

16. Have positive screening labs for human immunodeficiency virus (HIV), Hepatitis B and/or Hepatitis C

17. Have a positive urine drug test for alcohol, illicit drugs, or controlled substances other than those prescribed medications

18. Have previously participated in a clinical trial using COV795

19. Received any investigational drugs or devices in the past 4 weeks

20. History of spinal stenosis

21. Other criteria as specified in the trial protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Genova Clinical Research	Tucson	Arizona	United States	85704
2	Advanced Clinical Research Institute	Anaheim	California	United States	92801
3	Orange County Research Institute	Anaheim	California	United States	92801
4	United Clinical Research Center, Inc.	Anaheim	California	United States	92804
5	Associated Pharmaceutical Research Center, Inc.	Buena Park	California	United States	90620
6	Catalina Research Institute, LLC	Chino	California	United States	91710
7	Synergy Escondido Clinical Research	Escondido	California	United States	92025
8	Convergys Clinical Research, Inc.	Fresno	California	United States	93726
9	Triwest Research Associates	La Mesa	California	United States	91942
10	Skyline Research, Inc.	Long Beach	California	United States	90806
11	Orthopedic Research Institute	Boynton Beach	Florida	United States	33472
12	Avail Clinical Research	DeLand	Florida	United States	32720
13	Eastern Research	Hialeah	Florida	United States	33013
14	Scientific Clinical Research, Inc.	North Miami	Florida	United States	33161
15	Clinical Neuroscience Solutions, Inc.	Orlando	Florida	United States	32806
16	Compass Research, LLC	Orlando	Florida	United States	32806
17	Compass Research East, LLC	Oviedo	Florida	United States	32765
18	Gold Coast Research LLC	Plantation	Florida	United States	33317
19	Accord Clinical Research, LLC	Port Orange	Florida	United States	32129
20	Sarasota Pain Medicine Research, LLC	Sarasota	Florida	United States	34238
21	Stedman Clinical Trials	Tampa	Florida	United States	33613
22	Drug Studies America	Marietta	Georgia	United States	30060
23	Better Health Clinical Research	Newnan	Georgia	United States	30265
24	Chicago Anesthesia Pain Specialists	Chicago	Illinois	United States	60657
25	MediSphere Medical Research Center, LLC	Evansville	Indiana	United States	47714
26	International Clinical Research Institute	Leawood	Kansas	United States	66211
27	Community Research	Crestview Hills	Kentucky	United States	41017
28	Commonwealth Biomedical Research, LLC	Madisonville	Kentucky	United States	42431
29	QUEST Research Institute	Bingham Farms	Michigan	United States	48025
30	Sundance Clinical Research	Saint Louis	Missouri	United States	63141
31	Quality Clinical Research	Omaha	Nebraska	United States	68114
32	Premier Research	Trenton	New Jersey	United States	08540
33	Peters Medical Research	High Point	North Carolina	United States	27262
34	The Center for Clinical Research	Winston-Salem	North Carolina	United States	27103
35	Hightop Medical Research Center/Hilltop Physicians Inc.	Cincinnati	Ohio	United States	45224
36	New Horizons Clinical Research	Cincinnati	Ohio	United States	45242
37	Community Research	Cincinnati	Ohio	United States	45245
38	Allegheny Pain Management	Altoona	Pennsylvania	United States	16602
39	FutureSearch Trials	Austin	Texas	United States	78731
40	Austin Diagnostic Clinic	Austin	Texas	United States	78758
41	KRK Medical Research	Dallas	Texas	United States	75230
42	Optimum Clinical Research, Inc.	Salt Lake City	Utah	United States	84102

Sponsors and Collaborators

• Mallinckrodt

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mallinckrodt
• ClinicalTrials.gov Identifier: NCT01451385
• Other Study ID Numbers: COV15000181
• First Posted: Oct 13, 2011
• Last Update Posted: Sep 18, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Osteoarthritis; Back Pain; Low Back Pain

Study Results

Participant Flow

Pre-assignment Detail	After a screening period of up to 14 days, enrolled participants began treatment

Arm/Group Title	All Participants
Arm/Group Description	All participants receive 2 tablets of COV795 every 12 hours for up to 35 days
Period Title: Overall Study
STARTED	376
COMPLETED	285
NOT COMPLETED	91

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	All participants receive 2 tablets of COV795 every 12 hours for up to 35 days
Overall Participants	376
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.2 (13.72)
Sex: Female, Male (Count of Participants)
Female	220 58.5%
Male	156 41.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	58 15.4%
Not Hispanic or Latino	318 84.6%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.3%
Asian	62 16.5%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	75 19.9%
White	237 63%
More than one race	0 0%
Unknown or Not Reported	1 0.3%
Modified Brief Pain Index - Short Form: Pain Intensity (score on a scale) [Mean (Standard Deviation) ]
Worst pain in last 24 hours	7.6 (1.32)
Least pain in last 24 hours	5.6 (1.94)
Average pain in the last 24 hours	6.7 (1.38)
Pain right now	6.7 (1.64)
Modified Brief Pain Inventory-Short Form: Percent Pain Relief from Medication (percentage pain relief from medication) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage pain relief from medication]	13.2 (21.93)
Modified Brief Pain Inventory-Short Form: Pain Interference Scores (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	5.4 (2.03)
Western Ontario and McMaster U. Scores for Participants With Osteoarthritis (OA) of the Hip or Knee (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	11.74 (2.971)
WOMAC Questionnaire for Participants With Osteoarthritis (OA) of the Hip or Knee: Stiffness Score (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	4.94 (1.254)
WOMAC Questionnaire for Participants With Osteoarthritis (OA) of the Hip or Knee: Physical Function (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	38.96 (9.863)
WOMAC Questionnaire for Participants With Osteoarthritis (OA) of the Hip or Knee: Total Score (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	55.63 (13.251)
Roland-Morris Low Back Pain and Disability Scores for Participants with Chronic Low Back Pain (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	10.9 (5.27)

Outcome Measures

1. Primary Outcome

Title	Summary of Adverse Events (AEs)
Description	Collection of AEs began with subject's signing of the informed consent form, continued throughout the trial, and ended 7 days following the last dose of study drug, or at early termination. Treatment emergent AEs (TEAEs) are AEs that occurred after the first dose of study drug. TEAEs leading to discontinuation include 2 subjects who died (deaths not related to study drug). Clinically significant changes in values from physical exam, vital signs, clinical laboratory tests, and pulse oximetry were included as treatment emergent adverse events (TEAEs).
Time Frame	5 Weeks

Outcome Measure Data

Analysis Population Description

All participants = safety population

Arm/Group Title	All Participants
Arm/Group Description	All participants receive 2 tablets of COV795 every 12 hours for up to 35 days
Measure Participants	376
Had any TEAE	235 62.5%
Had a Severe TEAE	17 4.5%
Had a TEAE related to study medication	200 53.2%
Had a Serious AE	4 1.1%
Died	2 0.5%
Had a TEAE leading to discontinuation	73 19.4%

2. Secondary Outcome

Title	Modified Brief Pain Index - Short Form: Pain Intensity
Description	Participants rate their pain on a score from 0=no pain to 10=pain as bad as you can imagine
Time Frame	at end of treatment (within 5 weeks)

Outcome Measure Data

Analysis Population Description

All participants = safety population with a score at end of treatment (week 5)

Arm/Group Title	All Participants
Arm/Group Description	All participants receive 2 tablets of COV795 every 12 hours for up to 35 days
Measure Participants	359
Worst pain in the last 24 hours	4.0 (2.58)
Least pain in last 24 hours	2.4 (2.13)
Average pain in the last 24 hours	3.2 (2.25)
Pain right now	2.8 (2.36)

3. Secondary Outcome

Title	Modified Brief Pain Index - Short Form: Percent Pain Relief From Medication
Description	Participants rate percent pain relief from medication on a scale from 0% (no relief) to 100% (complete relief)
Time Frame	at end of treatment (within 5 weeks)

Outcome Measure Data

Analysis Population Description

Safety population with a score at end of treatment

Arm/Group Title	All Participants
Arm/Group Description	All participants receive 2 tablets of COV795 every 12 hours for up to 35 days
Measure Participants	359
Mean (Standard Deviation) [percentage of relief from medication]	67.7 (28.47)

4. Secondary Outcome

Title	Modified Brief Pain Inventory-Short Form: Pain Interference Scores
Description	Participants answer several questions about how much the pain interferes with their quality of life. The answers range from 0 = no interference to 10=completely interferes, and the average score for all the questions is recorded.
Time Frame	at end of treatment (within 5 weeks)

Outcome Measure Data

Analysis Population Description

Safety population with a score at end of treatment

Arm/Group Title	All Participants
Arm/Group Description	All participants receive 2 tablets of COV795 every 12 hours for up to 35 days
Measure Participants	359
Mean (Standard Deviation) [score on a scale]	2.2 (2.22)

5. Secondary Outcome

Title	Western Ontario and McMaster Universities Arthritis Index (WOMAC) Questionnaire for Participants With Osteoarthritis (OA) of the Hip or Knee: Pain Score
Description	Disease-specific quality of life is assessed using the WOMAC questionnaire (48-hour version) for participants with osteoarthritis (OA) of the hip or knee. The WOMAC pain score ranges from 0 to 20, with higher scores representing worse pain.
Time Frame	End of treatment (within 5 weeks)

Outcome Measure Data

Analysis Population Description

Participants in the safety population with OA of the hip or knee and a score at end of treatment

Arm/Group Title	All Participants
Arm/Group Description	All participants receive 2 tablets of COV795 every 12 hours for up to 35 days
Measure Participants	134
Mean (Standard Deviation) [score on a scale]	6.22 (4.016)

6. Secondary Outcome

Title	WOMAC Questionnaire for Participants With Osteoarthritis (OA) of the Hip or Knee: Stiffness Score
Description	Disease-specific quality of life is assessed using the WOMAC questionnaire (48-hour version) for participants with osteoarthritis (OA) of the hip or knee. The WOMAC stiffness score ranges from 0 to 8, with higher scores representing worse stiffness.
Time Frame	End of treatment (within 5 weeks)

Outcome Measure Data

Analysis Population Description

Participants in the safety population with OA of the hip or knee and a score at end of treatment

Arm/Group Title	All Participants
Arm/Group Description	All participants receive 2 tablets of COV795 every 12 hours for up to 35 days
Measure Participants	134
Mean (Standard Deviation) [score on a scale]	2.84 (1.713)

7. Secondary Outcome

Title	WOMAC Questionnaire for Participants With Osteoarthritis (OA) of the Hip or Knee: Physical Function Score
Description	Disease-specific quality of life is assessed using the WOMAC questionnaire (48-hour version) for participants with osteoarthritis (OA) of the hip or knee. The WOMAC physical function score ranges from 0 to 68, with higher scores representing worse functional limitations.
Time Frame	End of treatment (within 5 weeks)

Outcome Measure Data

Analysis Population Description

Participants in the safety population with OA of the hip or knee and a score at end of treatment

Arm/Group Title	All Participants
Arm/Group Description	All participants receive 2 tablets of COV795 every 12 hours for up to 35 days
Measure Participants	134
Mean (Standard Deviation) [score on a scale]	21.30 (13.180)

8. Secondary Outcome

Title	WOMAC Questionnaire for Participants With Osteoarthritis (OA) of the Hip or Knee: Total Score
Description	Disease-specific quality of life is assessed using the WOMAC questionnaire (48-hour version) for participants with osteoarthritis (OA) of the hip or knee. The WOMAC total score ranges from 0 to 96, with higher scores representing worse pain/disability.
Time Frame	End of treatment (within 5 weeks)

Outcome Measure Data

Analysis Population Description

Participants in the safety population with OA of the hip or knee and a score at end of treatment

Arm/Group Title	All Participants
Arm/Group Description	All participants receive 2 tablets of COV795 every 12 hours for up to 35 days
Measure Participants	134
Mean (Standard Deviation) [score on a scale]	30.35 (18.450)

9. Secondary Outcome

Title	Roland-Morris Low Back Pain and Disability Scores for Participants With Chronic Low Back Pain
Description	Roland-Morris Low Back Pain and Disability Scores for participants with chronic low back pain range from 0 to 24, with higher scores representing greater disability.
Time Frame	End of treatment (within 5 weeks)

Outcome Measure Data

Analysis Population Description

Participants in the safety population with chronic low back pain and a score at end of treatment

Arm/Group Title	All Participants
Arm/Group Description	All participants receive 2 tablets of COV795 every 12 hours for up to 35 days
Measure Participants	224
Mean (Standard Deviation) [score on a scale]	6.1 (5.75)

Adverse Events

Time Frame	From screening to follow-up, up to 45 days
Adverse Event Reporting Description	All treatment-emergent AEs are listed in the table of Other (Not Including Serious) Adverse Events
Arm/Group Title	All Participants
Arm/Group Description	All participants receive 2 tablets of COV795 every 12 hours for up to 35 days
All Cause Mortality
	All Participants
	Affected / at Risk (%)	# Events
Total	2/376 (0.5%)
Serious Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	4/376 (1.1%)
Cardiac disorders
Atrial fibrillation	1/376 (0.3%)
Cardio-respiratory arrest	1/376 (0.3%)
Gastrointestinal disorders
Abdominal pain	1/376 (0.3%)
Injury, poisoning and procedural complications
Road traffic accident	1/376 (0.3%)
Other (Not Including Serious) Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	235/376 (62.5%)
Blood and lymphatic system disorders
Haemorrhagic diathesis	1/376 (0.3%)
Lymphocytosis	1/376 (0.3%)
Neutropenia	1/376 (0.3%)
Cardiac disorders
Atrial fibrillation	1/376 (0.3%)
Cardio-respiratory arrest	1/376 (0.3%)
Palpitations	2/376 (0.5%)
Ear and labyrinth disorders
Ear pain	1/376 (0.3%)
Tinnitus	1/376 (0.3%)
Vertigo	2/376 (0.5%)
Eye disorders
Diplopia	1/376 (0.3%)
Vision blurred	2/376 (0.5%)
Gastrointestinal disorders
Abdominal discomfort	4/376 (1.1%)
Abdominal pain	1/376 (0.3%)
Abdominal pain upper	1/376 (0.3%)
Abdominal tenderness	1/376 (0.3%)
Colonic polyp	1/376 (0.3%)
Constipation	42/376 (11.2%)
Dental caries	1/376 (0.3%)
Diarrhoea	5/376 (1.3%)
Dry mouth	10/376 (2.7%)
Dyspepsia	6/376 (1.6%)
Infrequent bowel movements	1/376 (0.3%)
Large intestinal ulcer	1/376 (0.3%)
Nausea	87/376 (23.1%)
Oesophageal spasm	1/376 (0.3%)
Vomiting	57/376 (15.2%)
General disorders
Chest discomfort	1/376 (0.3%)
Chills	1/376 (0.3%)
Crepitations	1/376 (0.3%)
Fatigue	8/376 (2.1%)
Feeling jittery	1/376 (0.3%)
Oedema peripheral	3/376 (0.8%)
Pain	1/376 (0.3%)
Thirst	1/376 (0.3%)
Hepatobiliary disorders
Cholelithiasis	1/376 (0.3%)
Infections and infestations
Body tinea	1/376 (0.3%)
Bronchitis	1/376 (0.3%)
Cellulitis	1/376 (0.3%)
Gastroenteritis	1/376 (0.3%)
Gastroenteritis salmonella	1/376 (0.3%)
Gastroenteritis viral	1/376 (0.3%)
Helicobacter infection	1/376 (0.3%)
Influenza	1/376 (0.3%)
Nasopharyngitis	2/376 (0.5%)
Pharyngitis streptococcal	1/376 (0.3%)
Sinusitis	4/376 (1.1%)
Upper respiratory tract infection	3/376 (0.8%)
Urinary tract infection	5/376 (1.3%)
Vaginal infection	1/376 (0.3%)
Injury, poisoning and procedural complications
Arthropod bite	1/376 (0.3%)
Contusion	3/376 (0.8%)
Excoriation	1/376 (0.3%)
Fall	2/376 (0.5%)
Gastroenteritis radiation	1/376 (0.3%)
Muscle strain	1/376 (0.3%)
Road traffic accident	1/376 (0.3%)
Wound	1/376 (0.3%)
Investigations
Alanine aminotransferase increased	2/376 (0.5%)
Aspartate aminotransferase increased	1/376 (0.3%)
Blood lactate dehydrogenase increased	1/376 (0.3%)
Blood pressure increased	1/376 (0.3%)
Blood uric acid increased	1/376 (0.3%)
Gamma-glutamyltransferase increased	1/376 (0.3%)
Hepatic enzyme increased	5/376 (1.3%)
Liver function test abnormal	2/376 (0.5%)
Metabolism and nutrition disorders
Decreased appetite	3/376 (0.8%)
Fluid retention	1/376 (0.3%)
Hypercholesterolaemia	1/376 (0.3%)
Hypokalaemia	1/376 (0.3%)
Increased appetite	1/376 (0.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/376 (0.5%)
Back pain	4/376 (1.1%)
Joint swelling	1/376 (0.3%)
Musculoskeletal stiffness	2/376 (0.5%)
Myalgia	4/376 (1.1%)
Neck pain	1/376 (0.3%)
Pain in extremity	1/376 (0.3%)
Nervous system disorders
Balance disorder	1/376 (0.3%)
Cognitive disorder	1/376 (0.3%)
Dizziness	56/376 (14.9%)
Dizziness postural	1/376 (0.3%)
Headache	19/376 (5.1%)
Memory impairment	1/376 (0.3%)
Migraine	2/376 (0.5%)
Sedation	4/376 (1.1%)
Somnolence	43/376 (11.4%)
Tremor	1/376 (0.3%)
Psychiatric disorders
Anxiety	3/376 (0.8%)
Confusional state	1/376 (0.3%)
Cyclothymic disorder	1/376 (0.3%)
Disorientation	2/376 (0.5%)
Dysphoria	1/376 (0.3%)
Euphoric mood	4/376 (1.1%)
Hypervigilance	1/376 (0.3%)
Insomnia	6/376 (1.6%)
Middle insomnia	1/376 (0.3%)
Mood altered	1/376 (0.3%)
Sleep disorder	2/376 (0.5%)
Withdrawal syndrome	1/376 (0.3%)
Renal and urinary disorders
Bladder discomfort	1/376 (0.3%)
Dysuria	2/376 (0.5%)
Leukocyturia	1/376 (0.3%)
Urinary hesitation	1/376 (0.3%)
Urine flow decreased	2/376 (0.5%)
Reproductive system and breast disorders
Erectile dysfunction	1/376 (0.3%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/376 (0.3%)
Cough	6/376 (1.6%)
Dyspnoea	1/376 (0.3%)
Hiccups	1/376 (0.3%)
Hypopnoea	1/376 (0.3%)
Nasal congestion	3/376 (0.8%)
Oropharyngeal pain	2/376 (0.5%)
Sinus congestion	1/376 (0.3%)
Throat irritation	1/376 (0.3%)
Skin and subcutaneous tissue disorders
Blister	1/376 (0.3%)
Cold sweat	1/376 (0.3%)
Dermatitis	1/376 (0.3%)
Heat rash	1/376 (0.3%)
Hyperhidrosis	2/376 (0.5%)
Night sweats	1/376 (0.3%)
Pruritus	27/376 (7.2%)
Pruritus generalised	2/376 (0.5%)
Rash erythematous	2/376 (0.5%)
Skin ulcer	1/376 (0.3%)
Urticaria	1/376 (0.3%)
Vascular disorders
Flushing	3/376 (0.8%)
Hot flush	6/376 (1.6%)
Hypertension	4/376 (1.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.