DSI: Joseph Saponaro

Altea Therapeutics Chronic Hip & Knee OA Pain Trial

Multi-center, Escalating Dose, Placebo controlled, Dose Response, Randomized, Parallel-design Study of a Hydromorphone Patch in the treatment of Chronic Pain due to Osteoarthritis.

Sponsor: Altea Therapeutics
Study Drug: Transdermal Hydromorphone Patch (Similar to: Dilaudid or Palladone)
Medical Monitor:
CRA:
Central IRB:
Central Lab:
Site #:
Investigator #:
Phase 2
Subjects 100/10 Sites = 10 Subjects per Site
Primary Objective -> Evaluate the effect of administering four doses of narcotic, (Doses A, B, C and D) of a Hydromorphone Skin Patch versus P (Placebo) in the treatment of moderate to severe Osteoarthritis Pain. (A is the Lowest & D the Highest dose).
AE’s were mild to moderate: HA, Nausea
Pt’s already on Opioids ? R in a 2:2:1 ratio to: A, B or P
Pt’s Opioid Naļve -> R in a 2:1 ratio to: either the lowest dose of the Study Drug, Dose A or Placebo
MS is the “escape” or rescue medication
All Pts will be required to remain at the randomized dose of study drug for the first week after which they will be allowed to escalate.
Dose escalations will be allowed once a week thereafter based on pain relief and use of rescue medication.
Pts will be allowed to escalate up to Dose D if required.
WOMAC -> Western Ontario and McMaster University Index for disease-specific assessment of Hip or Knee OA
(Assesses the three dimensions of Pain, Disability and Joint Stiffness where 0 is Worst or most severe pain & 96 Best or least pain)
Diary: evaluate daily pain severity on a 4 point scale

IC
Age: 30-80
3 month h/o Symptomatic OA Hip or Knee with Lequesne severity index ? 9 @ screening requiring NSAIDs, Analgesics or Narcotics
WOMAC < 60 at Baseline Visit
All non-opioid Analgesics & NSAIDs must have been discontinued for 5 or more half-lives prior to study drug administration on day 1
If previously on Opioids, Pts must be taking only MS to control the pain, at the time of drug administration on day 1

EC
Any Skin Disorder
RA or Ankylosing Spondylitis
Neuropathic, Congenital or Metabolic Joint Diseases, FM
+ FH Drug or ETOH abuse
No systemic corticosteroids within 4 weeks study drug administration on Day 1
No intra-articular administration of corticosteroids within 8 weeks prior to study drug administration on Day 1
Must d/c the following drugs 5 or more half-lives prior to drug administration on Day 1:
a) Phenothiazines,
b) Tricyclic Antidepressants
c) or other CNS Depressants

VS W Lab, ICF Screening, EKG, X-Ray
VB W -1 Urine Drug Screen
V1 W 1 Lab, Drug Screen, Apply First Patch
V2 W 2 RTC 1 Week
V4 W 4 Lab, EKG
VF W 5 End, Follow-up Visit

Equianalgesic Dosing
Opioid Interchange MS 30 – 80 mgm
Morphine Sulfate (Avinza, Kadian) 30 - 80
Hydrocodone (Lortab, Vicodin) 15 - 40
Propoxyphene (Darvocet) 225 - 600
Levorphanol (Levodromoran) 2 - 5
Hydromorphone (Dilaudid) 4 - 10
Codeine (Tylenol # 3) 90 - 250
Oxycodone (OxyIR, Oxycontin, Percocet) 15 - 40
Merperidine (Demerol 150 - 400
Methadone 10 - 27
Tramadol (Ultram) 300 – 800
Fentanyl (Duragesic Patch) 25 – 50
Palladone (Hydromorphone XL) 12mgm =Duragesic 50mcg = Oxycontin 40 (20 BID)
(Palladone is available as: 12, 16, 24, 32 mgm)

Kellgren-Lawrence X-Ray Grading Scale
Osteoarthritis Severity Grades for Knee and Hip Joints
Adapted from the Council for International Organizations of Medical Sciences 1963

Subjects are required to have radiographic evidence of Grade 2-4 osteoarthritis of the Hip or Knee. The Kellgren scale used for assessing OA, described below, must be applied to a radiograph of the joint as follows: (Required position: Knee Standing + Hip Supine.)

Knee Joint (Standing Knee)
0 Normal
1 Doubtful narrowing of joint space and possible osteophyte lipping
2 Definite osteophytes and possible narrowing of joint space
3 Moderate multiple osteophytes, definite narrowing of joint space and some sclerosis and some sclerosis and possible deformity of bone ends
4 Large osteophytes, marked narrowing of joint space, severe sclerosis and definite deformity of bone ends

Hip Joint (Supine Hip)
0 Normal
1 Possible narrowing
2 Definite narrowing of joint space inferiorly, definite osteophytes and slight sclerosis
3 Marked narrowing of joint space, slight osteophytes, some sclerosis and cyst formation and deformity of femoral head and acetabulum
4 Gross loss of joint space with sclerosis and cysts, marked deformity of femoral head and acetabulum and large osteophytes