Safety and Efficacy Study of ADL5859 in Participants With... | NCT00603265

Label	Type	Description	Intervention Names
ADL5859	Experimental	2 x 50 milligrams (mg) ADL5859 capsules administered orally once in the morning and once in the evening for 28 days	Drug: ADL5859
Duloxetine	Active Comparator	2 x 30 mg duloxetine capsules administered orally once in the morning and 2 placebo capsules filled with lactose administered orally once in the evening for 28 days	Drug: Duloxetine Drug: Placebo
Placebo	Placebo Comparator	2 placebo capsules filled with lactose administered orally once in the morning and once in the evening for 28 days	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
ADL5859	Drug		ADL5859
Duloxetine

Measure	Description	Time Frame
Change From Baseline in Mean Numeric Pain Rating Scale (NPRS) Score	The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain. The mean of the daily average scores were calculated from the NPRS pain assessments obtained up to 3 times per day over a 7-day period. Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with treatment group as a main factor and baseline NPRS score as a covariate. Change from Baseline = NPRS at baseline - NPRS at Week 4; a positive number in the LS mean indicates a reduction in pain intensity from baseline.	Baseline, Week 4

Measure	Description	Time Frame
Percentage of Responders	A responder was defined as a participant who showed a reduction in average pain (as measured by NPRS) of at least 30% from baseline to Week 4. The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain. The percentage of participants who qualified as responders is presented per treatment arm.	Baseline, Week 4

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male and female participants between 18 and 75 years of age, inclusive
Body weight of at least 45 kilograms (kg)
Diabetes mellitus (type I or II) that is documented to be under stable glycemic control over a period of at least 3 months, as indicated by a glycosylated hemoglobin (HbgAIC) of less than or equal to 12% and a stable dose of insulin or oral diabetic medication for 90 days prior to starting study medication
No change in diabetic medications is planned for the duration of the study
Evidence of symmetrical, bilateral pain in the lower extremities due to diabetic peripheral neuropathy (DPN)
Presence of daily pain due to DPN for at least 3 months
Score greater than or equal to 3 on the physical examination portion of the Michigan Neuropathy Screening Instrument (MNSI)
Average weekly pain score of greater than or equal to 4 on the numeric pain rating scale (NPRS) for symmetrical neuropathic pain in the feet and legs
For male participants, be surgically sterile or agree to use an appropriate method of contraception
For female participants of childbearing potential, be surgically sterile or using an intrauterine device, or injectable, transdermal, or combination oral contraceptive deemed highly effective by the Food and Drug Administration (FDA)
Be willing and able to comply with the protocol requirements
Be able to understand and willing to provide written informed consent in English

Exclusion Criteria:

Presence of pain conditions that cannot be distinguished from DPN
Presence of significant renal disease, as indicated by a serum creatinine greater than or equal to 2.0 milligrams per deciliter (mg/dL), or presence of significant hepatic disease
Have a history of a seizure disorder
Presence of serious or unstable cardiovascular disease, respiratory disease, hematologic illness, or a psychiatric condition
History of evidence of symptomatic orthostatic hypotension
History of a major depressive disorder, generalized anxiety disorder, eating disorder, or substance abuse (including alcohol) within the past year
History or evidence of mania, bipolar disorder, or psychosis
History of allergy to acetaminophen or duloxetine
Score of greater than or equal to 18 on the Beck Depression Inventory II (BDI-II) or score of greater than zero on Item 9 of the BDI-II
Use of any of the following concomitant medications: fluvoxamine; quinolone antimicrobials (ciprofloxacin and enoxacin); selective serotonin reuptake inhibitors (SSRIs); serotonin norepinephrine reuptake inhibitors (SNRIs); tricyclic antidepressants; opioids; nonsteroidal anti-inflammatory drugs (NSAIDS); anticonvulsants; aspirin (with the exception of low-dose aspirin as cardiovascular prophylaxis); or cytochrome P4503A (CYP3A) and P-glycoprotein transporter inhibitors
Pregnant, lactating, or plans to become pregnant during the study
Presence of foot or toe amputation
Participation in another study with an investigational compound within the previous 30 days prior to study medication administration, or concurrent participation in another clinical study

Name	Affiliation	Role
Bruce Berger, MD	Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Integrated Research Group		Riverside	California	92506	United States
Torrance Clinical Research

ID	Title	Description
FG000	ADL5859	2 x 50 milligrams (mg) ADL5859 capsules administered orally once in the morning and once in the evening for 28 days
FG001	Duloxetine	2 x 30 mg duloxetine capsules administered orally once in the morning and 2 placebo capsules filled with lactose administered orally once in the evening for 28 days

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Mean Numeric Pain Rating Scale (NPRS) Score

The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain. The mean of the daily average scores were calculated from the NPRS pain assessments obtained up to 3 times per day over a 7-day period. Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with treatment group as a main factor and baseline NPRS score as a covariate. Change from Baseline = NPRS at baseline - NPRS at Week 4; a positive number in the LS mean indicates a reduction in pain intensity from baseline.

All participants who received at least 1 dose of study medication and had evaluable NPRS data. Baseline-observation-carried-forward (BOCF) was used to impute missing postbaseline values for participants who were discontinued from the study early.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, Week 4

ID	Title	Description
OG000	ADL5859	2 x 50 mg ADL5859 capsules administered orally once in the morning and once in the evening for 28 days
OG001	Duloxetine	2 x 30 mg duloxetine capsules administered orally once in the morning and 2 placebo capsules filled with lactose administered orally once in the evening for 28 days
OG002	Placebo	2 placebo capsules filled with lactose administered orally once in the morning and once in the evening for 28 days

Units	Counts
Participants	OG00075 OG00177 OG00272

Title

Denominators

Categories

Title	Measurements
	OG0001.02± 0.225 OG0011.74± 0.221 OG0021.51± 0.229

Secondary

Percentage of Responders

A responder was defined as a participant who showed a reduction in average pain (as measured by NPRS) of at least 30% from baseline to Week 4. The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain. The percentage of participants who qualified as responders is presented per treatment arm.

All participants who received at least 1 dose of study medication, completed the 4-week treatment period, and had evaluable NPRS data.

Posted

Number

percentage of participants

Baseline, Week 4

ID	Title	Description
OG000	ADL5859	2 x 50 mg ADL5859 capsules administered orally once in the morning and once in the evening for 28 days
OG001	Duloxetine	2 x 30 mg duloxetine capsules administered orally once in the morning and 2 placebo capsules filled with lactose administered orally once in the evening for 28 days
OG002	Placebo	2 placebo capsules filled with lactose administered orally once in the morning and once in the evening for 28 days

Secondary

Patient Global Impression of Change (PGIC)

PGIC is a participant-rated instrument that measures the change in the participant's overall status for the previous 2 weeks based on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). The number of participants in each category is presented.

All participants who received at least 1 dose of study medication, completed the 4-week treatment period, and had evaluable PGIC data.

Posted

Number

participants

Week 4

ID	Title	Description
OG000	ADL5859	2 x 50 mg ADL5859 capsules administered orally once in the morning and once in the evening for 28 days
OG001	Duloxetine	2 x 30 mg duloxetine capsules administered orally once in the morning and 2 placebo capsules filled with lactose administered orally once in the evening for 28 days
OG002	Placebo	2 placebo capsules filled with lactose administered orally once in the morning and once in the evening for 28 days

Units

Secondary

Change in Sleep Interference Scale (SIS) From Baseline

Sleep Interference was assessed on an 11-point Numeric Rating Scale where a score of 0 indicated "pain did not interfere with sleep" and a score of 10 indicated "pain completely interfered with sleep". Here, "n" signifies "Number of participants" for Baseline and Month 3 telephone interview whereas "n" signifies "number of observations" for Month 1, 2, and 3 because a participant could have had multiple visits during Month 1, 2, and 3 as this was a non-interventional study with no scheduled study visits, except Baseline visit and the Month 3 telephone interview. LS means were calculated using ANCOVA with treatment group as a main factor and baseline SIS score as a covariate. Change from baseline = SIS score at baseline - SIS score at Week 4.

All participants who received at least 1 dose of study medication, completed the 4-week treatment period, and had evaluable SIS data

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, Week 4

ID	Title	Description
OG000	ADL5859	2 x 50 mg ADL5859 capsules administered orally once in the morning and once in the evening for 28 days
OG001	Duloxetine	2 x 30 mg duloxetine capsules administered orally once in the morning and 2 placebo capsules filled with lactose administered orally once in the evening for 28 days
OG002

Secondary

Change From Baseline in the Evening Assessment of the 24-hour Overall Mean Pain Intensity Score

At each of the evening pain assessments, participants assessed their overall pain intensity over the preceding 24 hours using NPRS. The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain. The mean of the daily average scores were calculated from the NPRS pain assessments obtained at Baseline and Week 4. Change from baseline = NPRS at baseline - NPRS at Week 4.

All participants who received at least 1 dose of study medication and had evaluable 24-hour NPRS data.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Week 4

ID	Title	Description
OG000	ADL5859	2 x 50 mg ADL5859 capsules administered orally once in the morning and once in the evening for 28 days
OG001	Duloxetine	2 x 30 mg duloxetine capsules administered orally once in the morning and 2 placebo capsules filled with lactose administered orally once in the evening for 28 days
OG002	Placebo	2 placebo capsules filled with lactose administered orally once in the morning and once in the evening for 28 days

Secondary

Change From Baseline in NPRS at Rest in the Clinic

The mean of the daily average scores were calculated from the NPRS pain assessments obtained 1 time per week over a 4-week period. NPRS assessments were taken while the participant was at rest. The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain. LS means were calculated using ANCOVA with treatment group as a main factor and baseline NPRS score as a covariate. Change from baseline = NPRS at baseline - NPRS at Weeks 1, 2, 3, and 4.

All participants who received at least 1 dose of study medication, completed the 4-week treatment period, and had evaluable at-rest NPRS data.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, Week 1, Week 2, Week 3, Week 4

ID	Title	Description
OG000	ADL5859	2 x 50 mg ADL5859 capsules administered orally once in the morning and once in the evening for 28 days
OG001	Duloxetine	2 x 30 mg duloxetine capsules administered orally once in the morning and 2 placebo capsules filled with lactose administered orally once in the evening for 28 days
OG002	Placebo	2 placebo capsules filled with lactose administered orally once in the morning and once in the evening for 28 days

Secondary

Change From Baseline in NPRS After Walking 50 Feet in the Clinic

The mean of the daily average scores were calculated from the NPRS pain assessments obtained 1 time per week over a 4-week period. NPRS assessments were taken after the participant walked 50 feet in the clinic. The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain. LS means were calculated using ANCOVA with treatment group as a main factor and baseline NPRS score as a covariate. Change from baseline = NPRS at baseline - NPRS at Weeks 1, 2, 3, and 4.

All participants who received at least 1 dose of study medication, completed the 4-week treatment period, and had evaluable post-walk NPRS data.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, Week 1, Week 2, Week 3, Week 4

ID	Title	Description
OG000	ADL5859	2 x 50 mg ADL5859 capsules administered orally once in the morning and once in the evening for 28 days
OG001	Duloxetine	2 x 30 mg duloxetine capsules administered orally once in the morning and 2 placebo capsules filled with lactose administered orally once in the evening for 28 days
OG002	Placebo	2 placebo capsules filled with lactose administered orally once in the morning and once in the evening for 28 days

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Thrombocytopenia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 affected75 at risk EG0010 affected78 at risk EG0020 affected72 at risk
Atrioventricular block first degree	Cardiac disorders	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Bradycardia	Cardiac disorders	Systematic Assessment	EG0001 affected75 at risk EG0010 affected78 at risk EG0020 affected72 at risk
Bundle branch block	Cardiac disorders	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Palpitations	Cardiac disorders	Systematic Assessment	EG0001 affected75 at risk EG0012 affected78 at risk EG0021 affected72 at risk
Ventricular extrasystoles	Cardiac disorders	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Ear pain	Ear and labyrinth disorders	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Tinnitus	Ear and labyrinth disorders	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Vertigo	Ear and labyrinth disorders	Systematic Assessment	EG0001 affected75 at risk EG0010 affected78 at risk EG0020 affected72 at risk
Keratitis	Eye disorders	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Retinopathy	Eye disorders	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Visual acuity reduced	Eye disorders	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Abdominal distension	Gastrointestinal disorders	Systematic Assessment	EG0001 affected75 at risk EG0010 affected78 at risk EG0020 affected72 at risk
Abdominal pain lower	Gastrointestinal disorders	Systematic Assessment	EG0001 affected75 at risk EG0010 affected78 at risk EG0020 affected72 at risk
Abdominal pain upper	Gastrointestinal disorders	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment	EG0002 affected75 at risk EG0013 affected78 at risk EG0021 affected72 at risk
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG0004 affected75 at risk EG0019 affected78 at risk EG0023 affected72 at risk
Dry mouth	Gastrointestinal disorders	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Dysgeusia	Gastrointestinal disorders	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Erosive oesophagitis	Gastrointestinal disorders	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0001 affected75 at risk EG00116 affected78 at risk EG0023 affected72 at risk
Stomach discomfort	Gastrointestinal disorders	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0001 affected75 at risk EG0012 affected78 at risk EG0020 affected72 at risk
Asthenia	General disorders	Systematic Assessment	EG0001 affected75 at risk EG0013 affected78 at risk EG0021 affected72 at risk
Fatigue	General disorders	Systematic Assessment	EG0001 affected75 at risk EG0013 affected78 at risk EG0023 affected72 at risk
Feeling hot	General disorders	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Non-cardiac chest pain	General disorders	Systematic Assessment	EG0001 affected75 at risk EG0010 affected78 at risk EG0020 affected72 at risk
Oedema peripheral	General disorders	Systematic Assessment	EG0001 affected75 at risk EG0012 affected78 at risk EG0022 affected72 at risk
Seasonal allergy	Immune system disorders	Systematic Assessment	EG0001 affected75 at risk EG0010 affected78 at risk EG0020 affected72 at risk
Bronchitis	Infections and infestations	Systematic Assessment	EG0001 affected75 at risk EG0010 affected78 at risk EG0022 affected72 at risk
Cellulitis	Infections and infestations	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Gastroenteritis	Infections and infestations	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Gastroenteritis viral	Infections and infestations	Systematic Assessment	EG0001 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Labyrinthitis	Infections and infestations	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Lower respiratory tract infection	Infections and infestations	Systematic Assessment	EG0001 affected75 at risk EG0010 affected78 at risk EG0020 affected72 at risk
Nasopharyngitis	Infections and infestations	Systematic Assessment	EG0001 affected75 at risk EG0010 affected78 at risk EG0023 affected72 at risk
Onychomycosis	Infections and infestations	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Oral herpes	Infections and infestations	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Pharyngitis	Infections and infestations	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Sinusitis	Infections and infestations	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Upper respiratory tract infection	Infections and infestations	Systematic Assessment	EG0001 affected75 at risk EG0011 affected78 at risk EG0022 affected72 at risk
Urinary tract infection	Infections and infestations	Systematic Assessment	EG0002 affected75 at risk EG0012 affected78 at risk EG0022 affected72 at risk
Viral infection	Infections and infestations	Systematic Assessment	EG0001 affected75 at risk EG0010 affected78 at risk EG0020 affected72 at risk
Vulvovaginal mycotic infection	Infections and infestations	Systematic Assessment	EG0001 affected35 at risk EG0010 affected39 at risk EG0020 affected27 at risk
Contusion	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 affected75 at risk EG0010 affected78 at risk EG0020 affected72 at risk
Fall	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Limb injury	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Muscle strain	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Post-traumatic pain	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 affected75 at risk EG0010 affected78 at risk EG0020 affected72 at risk
Alanine aminotransferase increased	Investigations	Systematic Assessment	EG0001 affected75 at risk EG0010 affected78 at risk EG0020 affected72 at risk
Blood creatinine increased	Investigations	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Blood glucose increased	Investigations	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0021 affected72 at risk
Blood potassium increased	Investigations	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Blood urea increased	Investigations	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Eosinophil count increased	Investigations	Systematic Assessment	EG0003 affected75 at risk EG0010 affected78 at risk EG0020 affected72 at risk
Haematocrit decreased	Investigations	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Haemoglobin decreased	Investigations	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Red blood cell count decreased	Investigations	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Anorexia	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Decreased appetite	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected75 at risk EG0013 affected78 at risk EG0021 affected72 at risk
Hypoglycaemia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 affected75 at risk EG0012 affected78 at risk EG0020 affected72 at risk
Back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 affected75 at risk EG0011 affected78 at risk EG0021 affected72 at risk
Bursitis	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0023 affected72 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 affected75 at risk EG0010 affected78 at risk EG0020 affected72 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Tendonitis	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Dizziness	Nervous system disorders	Systematic Assessment	EG0001 affected75 at risk EG0015 affected78 at risk EG0020 affected72 at risk
Dysarthria	Nervous system disorders	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Essential tremor	Nervous system disorders	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Headache	Nervous system disorders	Systematic Assessment	EG0004 affected75 at risk EG0016 affected78 at risk EG0022 affected72 at risk
Hypoaesthesia	Nervous system disorders	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Somnolence	Nervous system disorders	Systematic Assessment	EG0000 affected75 at risk EG0013 affected78 at risk EG0020 affected72 at risk
Tremor	Nervous system disorders	Systematic Assessment	EG0000 affected75 at risk EG0013 affected78 at risk EG0020 affected72 at risk
Abnormal dreams	Psychiatric disorders	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0022 affected72 at risk
Anxiety	Psychiatric disorders	Systematic Assessment	EG0001 affected75 at risk EG0010 affected78 at risk EG0022 affected72 at risk
Confusional state	Psychiatric disorders	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Depression	Psychiatric disorders	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Insomnia	Psychiatric disorders	Systematic Assessment	EG0000 affected75 at risk EG0012 affected78 at risk EG0022 affected72 at risk
Micturition urgency	Renal and urinary disorders	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Pollakiuria	Renal and urinary disorders	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Proteinuria	Renal and urinary disorders	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Renal failure	Renal and urinary disorders	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Urinary incontinence	Renal and urinary disorders	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Libido decreased	Reproductive system and breast disorders	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Ovarian cyst	Reproductive system and breast disorders	Systematic Assessment	EG0000 affected35 at risk EG0010 affected39 at risk EG0021 affected27 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 affected75 at risk EG0010 affected78 at risk EG0020 affected72 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Nasal inflammation	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Throat irritation	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected75 at risk EG0010 affected78 at risk EG0020 affected72 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Cold sweat	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Dry skin	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 affected75 at risk EG0010 affected78 at risk EG0020 affected72 at risk
Dyshidrosis	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 affected75 at risk EG0010 affected78 at risk EG0020 affected72 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected75 at risk EG0012 affected78 at risk EG0020 affected72 at risk
Pruritus	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 affected75 at risk EG0010 affected78 at risk EG0023 affected72 at risk
Rash	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Rash erythematous	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0022 affected72 at risk
Urticaria	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected75 at risk EG0010 affected78 at risk EG0021 affected72 at risk
Hypertension	Vascular disorders	Systematic Assessment	EG0002 affected75 at risk EG0010 affected78 at risk EG0020 affected72 at risk
Hypotension	Vascular disorders	Systematic Assessment	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Orthostatic hypotension	Vascular disorders	Systematic Assessment	EG0007 affected75 at risk EG0016 affected78 at risk EG0026 affected72 at risk

ID	Term
D010523	Peripheral Nervous System Diseases
D009437	Neuralgia

ID	Term
D009468	Neuromuscular Diseases
D009422	Nervous System Diseases
D010146	Pain
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
C532570	N,N-diethyl-4-(5-hydroxyspiro(chromene-2,4'-piperidine)-4-yl)benzamide
D000068736	Duloxetine Hydrochloride

ID	Term
D013876	Thiophenes
D013457	Sulfur Compounds
D009930	Organic Chemicals
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds

ID	Title	Description
BG000	ADL5859	2 x 50 mg ADL5859 capsules administered orally once in the morning and once in the evening for 28 days
BG001	Duloxetine	2 x 30 mg duloxetine capsules administered orally once in the morning and 2 placebo capsules filled with lactose administered orally once in the evening for 28 days
BG002	Placebo	2 placebo capsules filled with lactose administered orally once in the morning and once in the evening for 28 days
BG003	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	ADL5859	2 x 50 mg ADL5859 capsules administered orally once in the morning and once in the evening for 28 days	0	75	27	75
EG001	Duloxetine	2 placebo capsules filled with lactose administered orally once in the morning and once in the evening for 28 days	1	78	28	78
EG002	Placebo	2 x 30 mg duloxetine capsules administered orally once in the morning and 2 placebo capsules filled with lactose administered orally once in the evening for 28 days	0	72	27	72

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Iron Deficiency Anaemia	Blood and lymphatic system disorders		Systematic Assessment		EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk
Arrhythmia	Cardiac disorders		Systematic Assessment	Resulted in one death in the duloxetine group.	EG0000 affected75 at risk EG0011 affected78 at risk EG0020 affected72 at risk