Phase 1
Completed N=59
Multiple Dose Escalation Study In Medically Stable Subjects With Psoriasis
Psoriasis · Immunomodulation
Source: ClinicalTrials.gov NCT01736696 ↗
Enrolled (actual)
59
Serious AEs
1.7%
Results posted
Feb 2013
Primary outcomePrimary: Change From Baseline in QT Interval at 1 Hour Post Morning Dose (HPD 1) on Day 1 — 372.20; 348.47; 369.40; 375.74 millisecond (msec)
Summary
This study was conducted in subjects with psoriasis to evaluate drug activity in this patient population by analysis of changes in psoriatic lesion biopsy characteristics. This subject population was selected to evaluate potentially relevant biological activity of CP-690,550 as well as assessing safety and pharmacokinetics.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in QT Interval at 1 Hour Post Morning Dose (HPD 1) on Day 1 |
372.20; 348.47; 369.40; 375.74; 383.96; 371.29 | — |
| PRIMARY Change From Baseline in QT Interval at 2 Hour Post Morning Dose (HPD 2) on Day 1 |
369.67; 350.27; 372.87; 377.48; 387.00; 374.00 | — |
| PRIMARY Change From Baseline in QT Interval at 4 Hour Post Morning Dose (HPD 4) on Day 1 |
373.73; 348.07; 373.20; 373.15; 381.44; 381.17 | — |
| PRIMARY Change From Baseline in QT Interval at 8 Hour Post Morning Dose (HPD 8) on Day 1 |
364.13; 356.73; 366.90; 374.56; 378.15; 372.25 | — |
| PRIMARY Change From Baseline in QT Interval at 12 Hour Post Morning Dose (HPD 12) on Day 1 |
371.73; 351.27; 372.63; 370.11; 379.78; 363.08 | — |
| PRIMARY Change From Baseline in QT Interval at 16 Hour Post Morning Dose (HPD 16) on Day 1 |
377.15; 345.44; 11.19; 13.11 | — |
| PRIMARY Change From Baseline in QT Interval at 0 Hour Post Morning Dose (HPD 0) on Day 14 |
374.80; 360.40; 367.70; 372.81; 383.41; 367.50 | — |
| PRIMARY Change From Baseline in QT Interval at 1 Hour Post Morning Dose (HPD 1) on Day 14 |
-8.87; 22.27; 0.11; 2.81; -0.96; 0.71 | — |
| PRIMARY Change From Baseline in QT Interval at 2 Hour Post Morning Dose (HPD 2) on Day 14 |
-3.80; 18.67; -3.93; 6.89; -3.81; 2.46 | — |
| PRIMARY Change From Baseline in QT Interval at 4 Hour Post Morning Dose (HPD 4) on Day 14 |
-13.80; 6.53; -8.41; 18.96; 9.59; -4.79 | — |
| PRIMARY Change From Baseline in QT Interval at 8 Hour Post Morning Dose (HPD 8) on Day 14 |
-9.33; -0.53; -6.15; -1.96; 4.85; -2.67 | — |
| PRIMARY Change From Baseline in QT Interval at 12 Hour Post Morning Dose (HPD 12) on Day 14 |
-13.47; 8.00; -10.52; 0.81; -7.44; -0.63 | — |
| PRIMARY Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval |
0; 1; 2; 1; 3; 2 | — |
| PRIMARY Number of Participants With Corrected QT (QTc) Interval Greater Than or Equal to 500 Millisecond |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) at Day 1 |
161; 349; 732; 860; 2120; 1720 | — |
| PRIMARY Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) at Day 14 |
154; 422; 850; 1350; 2600; 1780 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) at Day 1 |
48.3; 90.5; 212; 180; 457; 429 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) at Day 14 |
50.9; 87.7; 194; 225; 568; 403 | — |
| PRIMARY Time to Reach Maximum Observed Plasma Concentration (Tmax) at Day 1 |
0.50; 0.50; 0.50; 0.50; 1.00; 1.00 | — |
| PRIMARY Time to Reach Maximum Observed Plasma Concentration (Tmax) at Day 14 |
0.50; 1.00; 0.50; 1.00; 1.00; 1.00 | — |
| PRIMARY Accumulation Ratio (R0) |
0.974; 1.22; 1.22; 1.62; 1.16; 1.14 | — |
| PRIMARY Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 1 |
-14.39; 12.02; 1.17; 12.44; 8.38; 12.83 | — |
| PRIMARY Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 2 |
8.88; 34.74; 23.93; 46.07; 14.05; 52.43 | — |
| PRIMARY Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 4 |
-15.29; 51.71; 29.11; 71.55; 34.28; 32.81 | — |
| PRIMARY Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 7 |
5.72; 28.15; 13.47; 25.51; 1.61; 34.77 | — |
| PRIMARY Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 10 |
5.70; 8.76; 12.47; 36.76; 11.30; 12.61 | — |
| PRIMARY Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 14 |
1.01; 26.93; 7.07; 14.91; 10.74; 12.69 | — |
| PRIMARY Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 18 |
13.89; -14.04; -10.24; -10.65; -14.54; -46.69 | — |
| PRIMARY Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 21 |
-25.48; -6.38; -42.27; -14.82; -7.93; -27.37 | — |
| PRIMARY Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 28 |
-18.11; 9.29; 0.38; -4.60; -7.60; -22.08 | — |
| PRIMARY Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 42 |
-20.79; -15.72; -11.58; -1.60; -9.17; -1.63 | — |
| PRIMARY Change From Baseline in Immune Cell Function at Day 14 |
222.75; 205.40; 429.00; 406.11; 210.56; 252.50 | — |
| PRIMARY Change From Baseline in Reticulocyte Count at Day 2 |
124.00; 94.00; 81.50; 95.22; 80.56; 79.75 | — |
| PRIMARY Change From Baseline in Reticulocyte Count at Day 4 |
-14.00; -7.60; 17.33; -48.44; -14.67; -20.00 | — |
| PRIMARY Change From Baseline in Reticulocyte Count at Day 7 |
-3.40; 6.40; 17.11; -14.44; 3.22; -30.38 | — |
| PRIMARY Change From Baseline in Reticulocyte Count at Day 10 |
-16.40; -14.00; 16.00; -18.22; 6.56; -29.50 | — |
| PRIMARY Change From Baseline in Reticulocyte Count at Day 15 |
-24.00; -11.40; -8.56; -42.22; 24.11; -31.57 | — |
| PRIMARY Change From Baseline in Reticulocyte Count at Day 21 |
-13.40; 17.60; 44.22; 5.44; 40.25; -9.17 | — |
| PRIMARY Change From Baseline in Reticulocyte Count at Day 28 |
-16.20; 47.60; 49.56; 23.89; 21.75; 56.00 | — |
| PRIMARY Change From Baseline in Reticulocyte Count at Day 42 |
-4.60; -7.00; 34.56; -3.67; -2.33; 22.50 | — |
| PRIMARY Time to Reach Maximum Change From Baseline and Time to Return to Baseline Value for Fluorescence-Activated Cell Sorting (FACS), Reticulocyte Counts and Immune Cell Function |
— | — |
| PRIMARY Half Maximal Effective Area Under the Concentration-Time Curve 50 (EAUC 50) |
2696 | — |
| SECONDARY Number of Participants With Modified Psoriasis Severity Index (mPASI) at Day 14 |
1; 0; 0; 2; 2; 4 | — |
| SECONDARY Number of Participants With Physician's Global Assessment (PGA) of Psoriasis |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Gene Expression in Psoriatic Plaque Biopsies |
0.47; 0.36; 2.29; 1.16; 0.83; 0.68 | — |
| SECONDARY Immunohistochemistry From Psoriatic Plaque Biopsies |
115.00; 108.00; 122.50; 124.50; 189.00; 135.00 | — |
| SECONDARY Number of Participants With Keratin 16 (K16) Expression |
1; 1; 4; 2; 1; 1 | — |
| SECONDARY Number of Participants With Intracellular Adhesion Molecule (ICAM-1) by Epidermal Keratinocytes Expression |
— | — |
| SECONDARY Gene Expression in Peripheral Blood |
0.69; 0.99; 1.58; 2.06; 1.16; 1.46 | — |
Eligibility Criteria
Inclusion Criteria
- Male and/or female subjects between the ages of 18 and 65 years, inclusive, with active psoriasis lesion(s).
- Subjects should be healthy with the exception of psoriasis, where healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination. Blood pressure must be 50 kg (110 lbs)
- The following laboratory variables must be no more than 10% below the lower limit of the normal reference range: RBC, hemoglobin, hematocrit, WBC, absolute neutrophil count. The absolute lymphocyte count must be greater than or equal to the lower limit of the reference range. Values for AST, ALT, bilirubin and alkaline phosphatase must be no more than 10% above the upper limit of the normal reference range. Values for total cholesterol and LDL must be no more than 20% above the upper limit of the normal reference range except for subjects being treated for hyperlipidemia. Normal glomerular filtration rate (> 80 mL/min).
Exclusion Criteria
- Subjects with evidence or history of clinically significant hematological, renal, urological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic disorder.
- Subjects with controlled essential hypertension and/or hyperlipidemia may be eligible for the study provided that any medications that are administered.
- Screening 12-lead ECG demonstrating at least one of the following: heart rate > 100 bpm, QRS >120 msec, QTc > 430 msec (males), QTc > 450 msec (females) or PR > 220 msec.
- Abnormal chest radiographs including, but not limited to, evidence of past or present tuberculosis infection. History of tuberculosis without treatment and/or positive tuberculin reaction without known vaccination with BCG.
- Subjects with a history of tumors with the exception of adequately treated basal cell carcinoma of the skin.
Data sourced from ClinicalTrials.gov (NCT01736696). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.