Efficacy and Safety of Adalimumab in Patients With Psoriasis and Obstructive Sleep Apnea

This study has been completed.
Sponsor:
Collaborator:
Abbott
Information provided by (Responsible Party):
Innovaderm Research Inc.
ClinicalTrials.gov Identifier:
NCT01181570
First received: August 11, 2010
Last updated: October 27, 2011
Last verified: October 2011
  Purpose

This study will evaluate the effect and safety of adalimumab in approximately 20 subjects with mild to moderate psoriasis and sleep apnea and will be conducted in one treatment center located in Montreal.

Patients with psoriasis often have additional disorders such as obesity. Obese patients are more at risk of developing obstructive sleep apnea. This is believed to be caused by both the collapse of upper airways and inflammation (swelling). Adalimumab, a drug currently approved by Health Canada for the treatment of psoriasis, blocks tumor necrosis factor-alpha (TNF-alpha). This chemical is present at higher levels in patients with sleep apnea. It is believed that adalimumab could improve obstructive sleep apnea by lowering the levels of TNF-alpha.


Condition Intervention Phase
Psoriasis
Sleep Apnea, Obstructive
Drug: Adalimumab
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Adalimumab in Patients With Psoriasis and Obstructive Sleep Apnea

Resource links provided by NLM:


Further study details as provided by Innovaderm Research Inc.:

Primary Outcome Measures:
  • Number of sleep apnea per hour. [ Time Frame: 56 Days ] [ Designated as safety issue: No ]
    Changes from baseline in number of apnea/hypopnea per hour for patients with psoriasis randomized to adalimumab as compared to patients randomized to topical therapy.


Secondary Outcome Measures:
  • Sleep maintenance efficiency [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    Changes from baseline in sleep maintenance efficiency for patients with psoriasis randomized to adalimumab as compared to patients randomized to placebo.

  • Total wake time [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    Changes from baseline in total wake time for patients with psoriasis randomized to adalimumab as compared to patients randomized to placebo

  • Percentage of sleep time [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    Changes from baseline in percentage of sleep time for patients with psoriasis randomized to adalimumab as compared to patients randomized to placebo.

  • Time spent in REM (rapid eye movement) stage. [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    Changes from baseline in time spent in REM (rapid eye movement) stage for patients with psoriasis randomized to adalimumab as compared to patients randomized to placebo.

  • Time spent in sleep stage N1 [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    Changes from baseline in time spent in sleep stages N1 for patients with psoriasis randomized to adalimumab as compared to patients randomized to placebo.

  • Time spent in sleep stage N3 [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    Changes from baseline in time spent in sleep stage N3 for patients with psoriasis randomized to adalimumab as compared to patients randomized to placebo.

  • REM (rapid eye movement) latency time [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    Changes from baseline in REM (rapid eye movement) latency time for patients with psoriasis randomized to adalimumab as compared to patients randomized to placebo.

  • Minimum overnight oxygen saturation index [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    Changes from baseline in minimum overnight oxygen saturation index for patients with psoriasis randomized to adalimumab as compared to patients randomized to placebo.

  • Oxygen desaturation index [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    Changes from baseline in oxygen desaturation index for patients with psoriasis randomized to adalimumab as compared to patients randomized to placebo.

  • Sleep related quality of life questionnaire (FOSQ) [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    Changes from baseline in the sleep related quality of life questionnaire (FOSQ - functional outcome of sleep questionnaire) for patients with psoriasis randomized to adalimumab as compared to patients randomized to placebo.

  • Epworth sleepiness scale [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    Changes from baseline in patient's perception of daytime sleepiness as measured by the Epworth sleepiness scale for patients with psoriasis randomized to adalimumab as compared to patients randomized to placebo.

  • Daytime sleep latency [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    Changes from baseline in daytime sleep latency time for patients with psoriasis randomized to adalimumab as compared to patients randomized to placebo

  • Safety of adalimumab [ Time Frame: 56 weeks ] [ Designated as safety issue: Yes ]
    Evaluate the safety of adalimumab in patients with psoriasis randomized to adalimumab as compared to patients randomized to placebo.

  • Body surface area (BSA) [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    Tertiary - Changes from baseline in Body Surface Area (BSA) for patients with psoriasis randomized to adalimumab as compared to patients randomized to placebo.

  • Physician's Global Assessment (PGA) [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    Tertiary - Changes from baseline in Physician's Global Assessment (PGA) for patients with psoriasis randomized to adalimumab as compared to patients randomized to placebo.

  • Psoriatic Area and Severity Index (PASI) [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    Tertiary - Changes from baseline in Psoriatic Area and Severity Index (PASI) for patients with psoriasis randomized to adalimumab as compared to patients randomized to placebo.

  • PASI 75 (75% reduction in Psoriatic Area and Severity Index) [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    Tertiary - Proportion of patients who achieve PASI 75 (75% reduction in Psoriatic Area and Severity Index) at Day 56 for patients with psoriasis randomized to adalimumab as compared to patients randomized to placebo.

  • Proportion with PGA (Physician's Global Assessment) of 0 or 1 [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    Tertiary - Proportion of patients who achieve a PGA (Physician's Global Assessment) of 0 or 1 at Day 56 for patients with psoriasis randomized to adalimumab as compared to patients randomized to placebo.

  • Time to sleep induction [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    Changes from baseline in time to sleep induction for patients with psoriasis randomized to adalimumab as compared to patients randomized to placebo

  • Time spent in sleep stages N2 [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    Changes from baseline in time spent in sleep stages N2 for patients with psoriasis randomized to adalimumab as compared to patients randomized to placebo.


Enrollment: 20
Study Start Date: September 2010
Study Completion Date: September 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Adalimumab Drug: Adalimumab
Patients receive adalimumab 80 mg followed by 40 mg at week 1 and 40 mg every other week (EOW) thereafter.
Other Names:
  • Humira
  • mannitol
  • citric acid monohydrate
  • sodium citrate
  • disodium phosphate dihydrate
  • sodium dihydrogen phosphate dihydrate
  • sodium chloride
  • polysorbate 80
  • water for injection
  • sodium hydroxide.
Placebo Comparator: Placebo Drug: Placebo
Patients will receive 2 injections of placebo at week 0, one injection at week 1 and one injection every other week (EOW) thereafter.
Other Names:
  • mannitol
  • citric acid monohydrate
  • sodium citrate
  • disodium phosphate dihydrate
  • sodium dihydrogen phosphate dihydrate
  • sodium chloride
  • polysorbate 80
  • water for injection
  • sodium hydroxide

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men or women are 18 to 80 years of age at time of consent.
  • Has at least a 6-month history of chronic moderate to severe psoriasis and is a candidate for systemic therapy.
  • Has a body surface area (BSA) covered with psoriasis of at least 5% or more at Day 0.
  • Has a diagnosis of obstructive sleep apnea confirmed by at least 15 episodes/hour of apnea/hypopnea at the polysomnographic testing on Day -2.
  • Unless surgically sterile (or at least 1 year post-menopausal), or abstinent, patient (female) is willing to use an effective method of contraception for at least 30 (90 for "c") days before Day 0 and until at least 6 months after the last drug administration. Effective method of contraception are:

    • Condom with spermicidal foam, cream or gel, sponge with spermicidal foam, cream or gel, diaphragm with spermicidal foam, cream or gel
    • Intra uterine device (IUD)
    • Contraceptives (oral or parenteral)
    • Nuvaring
    • Vasectomised partner
    • Same-sex partner
  • Negative serum pregnancy test at the screening visit for female patient of childbearing potential only.
  • Patient is judged not to have contraindications to adalimumab as determined by the principal investigator based upon the results of medical history, laboratory profile, physical examination and chest X-ray performed at screening.
  • Patient will be evaluated for latent tuberculosis (TB) infection with a purified protein derivative (PPD) or a QuantiFERON-TB Gold test and Chest X-Ray (CXR). All patients who previously received TB immunization (BCG vaccination) will have the QuantiFERON-TB Gold test performed. Patient who demonstrates evidence of latent TB infection (either PPD more than or equal to 5 mm of induration or positive QuantiFERON-TB Gold) or suspicious CXR will not be allowed to participate.
  • Capable of giving informed consent and the consent must be obtained prior to any study related procedures.
  • Patient must be able and willing to self-administer subcutaneous (SC) injections or have a qualified person available to administer SC injections.

Exclusion Criteria:

  • Has received medical treatment for sleep apnea in the 6 months preceding Day 0.
  • Presence of other skin diseases or skin infections (bacterial, fungal or viral) that may interfere with evaluation of psoriasis or with patient's safety.
  • Has a history of an allergic reaction or significant sensitivity to constituents of study drug, including latex (a component of the pre-filled syringe).
  • Use of any non-biological systemic therapy for the treatment of psoriasis (including PUVA (psoralen and ultraviolet A)) less than 30 days before Day 0.
  • Use of investigational chemical agents within 30 days or five half-lives prior to Day 0, whichever is longer.
  • Use of any biological therapy for the treatment of psoriasis less than 90 days before Day 0.
  • Current use of oral or injectable corticosteroids or during the study. Inhaled corticosteroids for stable medical conditions are allowed.
  • Use of any topical treatments for psoriasis or phototherapy within two weeks prior to Day 0, at the exception of low strength (hydrocortisone and desonide) topical corticosteroid for the face, groin (including genitals) and inframammary areas.
  • Has received Anakinra/Kineret within the last 2 weeks prior to Day 0 or is likely to receive Anakinra/Kinaret during the course of the study.
  • Has a poorly controlled medical condition, such as uncontrolled diabetes, documented history of recurrent infections, unstable ischemic heart disease, congestive heart failure, recent stroke (within the past 90 days), chronic leg ulcer or any other condition which, in the opinion of the investigator, would put the patient at risk if participating in the study.
  • Has a history of neurologic symptoms suggestive of central nervous system (CNS) demyelinating disease (e.g. optic neuritis, visual disturbance, gait disorder/ataxia, facial paresis, apraxia).
  • Has a history of cancer or lymphoproliferative disease other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix.
  • Has a history of listeriosis, treated or untreated TB, persistent chronic infections, or recent active infections requiring hospitalization or treatment with intravenous anti-infectives within 30 days or oral anti-infectives within 14 days prior to Day 0.
  • Has received any live attenuated vaccine 28 days or less before Day 0 or plans to receive one during the study.
  • Has hepatitis B or hepatitis C viral infection.
  • Has any of the following: hemoglobin ≤ 10 g/L, white blood cell count ≤ 3.0 X 10^9/L, platelet count ≤130 X 10^9/L, ALT ≥ 3 times the upper limit of normal, AST ≥ 3 times the upper normal limit, total bilirubin ≥ 2 times the upper normal limit or creatinine ≥ 150 µmol/L.
  • Current use or plan to use anti-retroviral therapy at any time during the study.
  • Is known to have immune deficiency or is immunocompromised.
  • Current pregnancy or lactation or considering becoming pregnant during the study or for 150 days after the last dose of study medication.
  • Has a history of clinically significant drug or alcohol abuse in the last year.
  • Is considered by the investigator, for any reason, to be an unsuitable candidate for the study.
  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: NCT01181570

Locations
Canada, Quebec
Innovaderm Research Inc.
Montreal, Quebec, Canada, H2K 4L5
Sponsors and Collaborators
Innovaderm Research Inc.
Abbott
Investigators
Principal Investigator: Robert Bissonnette, MD, FRCPC Innovaderm Research Inc.
  More Information

No publications provided

Responsible Party: Innovaderm Research Inc.
ClinicalTrials.gov Identifier: NCT01181570     History of Changes
Other Study ID Numbers: Inno-6016, IMM 10-0005
Study First Received: August 11, 2010
Last Updated: October 27, 2011
Health Authority: Canada: Health Canada

Keywords provided by Innovaderm Research Inc.:
psoriasis
adalimumab
obstructive sleep apnea
obesity

Additional relevant MeSH terms:
Apnea
Psoriasis
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Dyssomnias
Nervous System Diseases
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms
Signs and Symptoms, Respiratory
Skin Diseases
Skin Diseases, Papulosquamous
Sleep Disorders
Sleep Disorders, Intrinsic
Adalimumab
Citric Acid
Mannitol
Anti-Inflammatory Agents
Anticoagulants
Antirheumatic Agents
Cardiovascular Agents
Chelating Agents
Diuretics
Diuretics, Osmotic
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sequestering Agents

ClinicalTrials.gov processed this record on October 30, 2014