Study of Dose-Effect of COL-121 Ointment in Patients With Plaque-Type Psoriasis

This study has been completed.
Sponsor:
Information provided by:
Deltanoid Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00625326
First received: February 20, 2008
Last updated: April 19, 2011
Last verified: April 2011
  Purpose

Low doses of topically administered vitamin D analogs have been shown to have an anti-psoriatic effect without the risk of hypercalcemia. Calcipotriol, the most thoroughly studied of the vitamin D analogs, was first approved in Europe in the early 1990s. It has been shown to be comparable or slightly more effective than class II corticosteroid ointments. However, patients had reduced levels of parathyroid hormone; mean serum and urine calcium were increased during treatment and hypercalciuria was observed. These effects were reversible with discontinuation of therapy. Thus, while calcipotriol ointment was shown to be effective, the potential for alterations in calcium homeostasis have limited its use to 100 g of ointment per week (0.5 mg calcipotriol/week). Work has continued on the creation of new vitamin D analogs, such as COL-121, with the intent of eliminating the adverse effects of hypercalcemia and hypercalciuria with a compound that is more stable and more easily administered.


Condition Intervention Phase
Plaque-type Psoriasis
Drug: COL-121
Drug: 50 µg/g Calcipotriene Ointment
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II Study of the Dose-Effect of COL-121 Ointment in Patients With Plaque-Type Psoriasis

Resource links provided by NLM:


Further study details as provided by Deltanoid Pharmaceuticals:

Primary Outcome Measures:
  • Physician's Global Assessment [ Time Frame: Randomization and Day 84 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from Baseline of PGA score [ Time Frame: Day 0, week 2, 4, 8, 12, and 16 ] [ Designated as safety issue: No ]
    PGA score is a scale from 0 to 5, with 0=clear and 5=very severe

  • Change from baseline of Psoriasis Signs Severity (PSS) [ Time Frame: Day 0, week 2, 4, 8, 12, and 16 ] [ Designated as safety issue: No ]
    Psoriasis Signs Severity (PSS) is the investigator's evaluation of the severity of each of three key signs of psoriasis (erythema, plaque elevation, and scaling). The PSS for a target plaque is the sum of the individual sign scores for that target plaque. The Erythema Severity Scale, Plaque Elevation Severity Scale, and the Scaling Severity Score are each assessed on a scale from 0=clear to 5=very severe. These scores combined = PSS.


Enrollment: 321
Study Start Date: January 2008
Study Completion Date: June 2009
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 75 µg/g COL-121 Ointment
75 µg/g COL-121 Ointment
Drug: COL-121
75 µg/g COL-121 Ointment
Experimental: 150 µg/g COL-121 Ointment
150 µg/g COL-121 Ointment
Drug: COL-121
150 µg/g COL-121 Ointment
Experimental: 300 µg/g COL-121 Ointment
300 µg/g COL-121 Ointment
Drug: COL-121
300 µg/g COL-121 Ointment
Active Comparator: 50 µg/g Calcipotriene Ointment
50 µg/g Calcipotriene Ointment (active control)
Drug: 50 µg/g Calcipotriene Ointment
50 µg/g Calcipotriene Ointment
Other Name: Dovonex
Placebo Comparator: Placebo Ointment
Placebo Ointment
Drug: Placebo
Placebo

Detailed Description:

Psoriasis affects more than 7 million Americans. Plaque-type psoriasis (the most common type of psoriasis) is an inflammatory skin condition with reactive abnormal epidermal differentiation and hyperproliferation. It is characterized by raised, thickened, plaques of erythematous skin covered by a silvery-white scale. Plaque-type psoriasis is most commonly found on the knees, elbows, and scalp but can appear anywhere on the body. While patients with psoriasis may complain of itchiness and discomfort, the psychological effects of the disease are the most debilitating. In a 1998 survey conducted by the National Psoriasis Foundation, it was found that 79% of the psoriasis patients surveyed reported that the disease had a negative impact on their lives and 40% felt frustrated with the ineffectiveness of their current therapies.

Although the exact cause of this skin disease is unknown, it is clear that immune-based inflammatory mechanisms initiate an accelerated growth of skin cells. This accelerated growth results in an agglomeration of skin cells on the surface of the epidermis that the body cannot shed. This agglomeration creates the thickened patches of scaly skin characteristic of the disease.

Clinical use of systemic vitamin D to treat psoriasis has been limited because of the induction of hypercalcemia. In contrast, low doses of topically administered vitamin D analogs have been shown to have an anti-psoriatic effect without the risk of hypercalcemia. Topical vitamin D analogs have the ability to inhibit the proliferation and promote the differentiation of keratinocytes in psoriatic skin. In addition, vitamin D analogs may also act by inhibiting cytokine production by keratinocytes or lymphocytes. Calcipotriol, the most thoroughly studied of the vitamin D analogs, was first approved in Europe in the early 1990s. It has been shown to be comparable or slightly more effective than class II corticosteroid ointments. In patients with extensive psoriasis, calcipotriol ointment was shown to be effective. However, patients had reduced levels of parathyroid hormone; mean serum and urine calcium were increased during treatment and hypercalciuria was recorded in 3 patients. These effects were reversible with discontinuation of therapy. In a review of the effects on calcium homeostasis, it was noted that calcipotriol (50 µg/g) had no effects on serum or urine calcium when administered at doses of 40-50 g/week and two reports of hypercalcemia at doses of 70-100 g/week. Thus, while calcipotriol ointment was shown to be effective, the potential for alterations in calcium homeostasis have limited its use to 100 g of ointment per week (0.5 mg calcipotriol/week). Subsequently, calcipotriol and tacalcitol, another vitamin D analog, have become first-line therapies in the management of "mild to moderate" psoriasis in several countries in Western Europe, Japan and the USA.

Work has continued on the creation of new vitamin D analogs, such as COL-121, with the intent of eliminating the adverse effects of hypercalcemia and hypercalciuria with a compound that is more stable and more easily administered.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Psoriasis must affect at least 2% and not more than 10% of the subject's body surface area, excluding the face and scalp
  • Subject must have 2 to 4 target plaques on the area to be treated, excluding the face and scalp.
  • Subjects who are women of childbearing potential must have a negative pregnancy test and be non-lactating.
  • Subjects who are women of childbearing potential must utilize one of the following methods of birth control throughout the study: IUD, diaphragm, a condom, a spermicidal gel or foam, oral contraceptives (provided subject has been utilizing this method for at least 4 months prior to Visit 1 and has not changed the brand within this period). Subjects may also participate if they are surgically sterilized, in a monogamous relationship with a sterile partner, or abstain from sexual intercourse during the course of the study.
  • Subjects must be in good general health and free of any disease state or physical condition that, in the investigator's opinion, may interfere with study evaluations or exposes the subject to unacceptable risk by study participation.
  • Subject must be willing and able to apply the study medication as directed, comply with the study instructions, and commit to all the follow-up visits for the duration of the study.
  • Subjects must sign an informed consent form.

Exclusion Criteria:

  • Subjects who have guttate, pustular, erythrodermic or other non-plaque types of psoriasis.
  • Subjects who have spontaneously improving or rapidly deteriorating plaque psoriasis.
  • Subjects who have used systemic immunomodulatory therapy known to affect psoriasis and to typically decrease immune cell populations (e.g., alefacept) within the previous 40 weeks.
  • Subjects who have used any systemic immunomodulatory therapy known to affect psoriasis and to NOT typically decrease immune cell populations (e.g., etanercept) within the previous 16 weeks.
  • Subjects who have used any photo-therapy (including laser), photo-chemotherapy or systemic psoriasis therapy (e.g., systemic corticosteroids, methotrexate, retinoids, cyclosporine) within the previous 12 weeks.
  • Subjects who have had prolonged exposure to natural or artificial sources of ultraviolet radiation within the previous 3 weeks or are intending to have such exposure during the study, thought by the investigator likely to modify the subject's plaque psoriasis.
  • Subjects who have used topical anti-psoriatic therapy (including topical retinoids) on the areas to be evaluated within the previous 2 weeks.
  • Subjects who have used emollients/moisturizers on the areas to be evaluated within the previous 1 day.
  • Subjects who have untreated bacterial, tubercular, fungal or viral lesions of the skin on the areas to be evaluated.
  • Subjects who have known sensitivity to a component of the study medication or to topical or systemic vitamin D.
  • Subjects who have any significant condition such as diseases of the hepatic, renal, endocrine, musculoskeletal, or nervous system, or any gross physical impairment.
  • Subjects who have taken a vitamin D supplement that exceeds 400 IU per day in the previous 30 days.
  • Subjects who have taken a calcium supplement that exceeds 1200 mg per day in the previous 30 days.
  • Subjects who are using lithium or Plaquenil.
  • Subjects who are using beta-blocking medication or thiazide diuretics whose dose has not been stable for at least 12 weeks.
  • Subjects who have a history of hypercalcemia or evidence of vitamin D toxicity.
  • Subjects who are currently being treated for malignancy or have been diagnosed with melanoma within the past 5 years.
  • Subjects who have received any investigational treatment(s) within the previous 30 days.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00625326

Locations
United States, California
East Bay Dermatology Medical Group
Fremont, California, United States, 94538
Dermatology Research Associates
Los Angeles, California, United States, 90045
Skin Surgery Medical Group, Inc.
San Diego, California, United States, 92117
Dermatology Specialists, Inc.
Vista, California, United States, 92083
United States, Colorado
Cherry Creek Research, Inc.
Denver, Colorado, United States, 80209
Longmont Medical Research Network
Longmont, Colorado, United States, 80501
United States, Connecticut
The Savin Center, PC
New Haven, Connecticut, United States, 06511
United States, Florida
International Dermatology Research, Inc.
Miami, Florida, United States, 33144
United States, Georgia
MedaPhase, Inc.
Newnan, Georgia, United States, 30263
United States, Kentucky
Dermatology Specialists
Louisville, Kentucky, United States, 40202
United States, Michigan
Michigan Center for Skin Care Research
Clinton Township, Michigan, United States, 48038
Grekin Skin Institute
Warren, Michigan, United States, 48088
United States, New Mexico
Academic Dermatology Associates
Albuquerque, New Mexico, United States, 87106
United States, Oregon
Northwest Cutaneous Research Specialists
Portland, Oregon, United States, 97210
United States, Pennsylvania
Philadelphia Institute of Dermatology
Flourtown, Pennsylvania, United States, 19034
United States, Texas
DermResearch, Inc.
Austin, Texas, United States, 78759
Dermatology Associates of San Antonio
San Antonio, Texas, United States, 78258
United States, Utah
Dermatology Research Center
Salt Lake City, Utah, United States, 84124
United States, Virginia
The Education & Research Foundation, Inc.
Lynchburg, Virginia, United States, 24501
United States, Washington
Premier Clinical Research
Spokane, Washington, United States, 99204
Sponsors and Collaborators
Deltanoid Pharmaceuticals
Investigators
Study Director: Michael Graeber, MD Galderma
  More Information

No publications provided

Responsible Party: Michael Graeber, Head of Global Clinical Project Management & US Development, Galderma
ClinicalTrials.gov Identifier: NCT00625326     History of Changes
Other Study ID Numbers: COL-121-PSOR-201
Study First Received: February 20, 2008
Last Updated: April 19, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Deltanoid Pharmaceuticals:
psoriasis

Additional relevant MeSH terms:
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Calcipotriene
Calcitriol
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions
Calcium Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasoconstrictor Agents
Cardiovascular Agents
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on August 21, 2014