Osteoarthritis of the Knee
Conditions
Keywords
osteoarthritis, knee, corticosteroid, intra-articular, injection
Brief summary
The purpose of this study was to evaluate the safety, pharmacokinetics and pharmacodynamics of FX006 in patients with osteoarthritis of the knee.
Detailed description
This study was a double-blind, randomized, parallel-group, active comparator design. The study was conducted in male and female patients ≥35 years of age with symptomatic OA of the knee. Twenty-four (24) patients with knee OA were randomized (1:1:1:1) and treated with a single IA injection of either 10, 40, or 60 mg of FX006 or 40 mg of TCA IR. Each patient was evaluated for a total of 6 weeks following a single IA injection. Following screening, safety, PK and pharmacodynamics (PD) were evaluated during one (1) 48-hour in-patient period (Day -1 to Day 2), two (2) 24-hour in-patient periods (Day 14-15 and Day 42-43) and seven (7) out-patient visits (Days 3, 4, 5, 8, 22, 29 and 36).
Interventions
DRUGFX006 10 mg
single 3 mL IA injection
DRUGFX006 40 mg
single 3 mL IA injection
DRUGFX006 60 mg
single 3 mL IA injection
DRUGTCA IR 40
single 1 mL IA injection
Sponsors
Pacira Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
35 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Willingness and ability to comply with the study procedures and visit schedules and ability to follow verbal and written instructions * Male or female \>=35 years of age * Diagnosis of unilateral or bilateral OA of the knee for at least 6 months prior to Screening with confirmation of OA according to American College of Rheumatology Criteria for Classification of Idiopathic OA of the Knee (clinical and radiological) based on an X-ray performed within 6 months prior to Screening or during the Screening period * Body mass index (BMI) ≤ 40 kg/m2 * Willingness to abstain from use of the protocol-specified restricted medications Main
Exclusion criteria
* History of Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease, sarcoidosis or amyloidosis * History of arthritides due to crystals (e.g., gout, pseudogout) * History of infection in the index joint * Clinical signs and symptoms of active knee infection or crystal disease of the index knee * Presence of surgical hardware or other foreign body in the index knee * Unstable joint (such as a torn anterior cruciate ligament) * IA corticosteroid (investigational or marketed) in any joint within 3 months of Screening * IA hyaluronic acid (investigational or marketed) in the index knee within 6 months of Screening * Oral, inhaled or intranasal corticosteroids (investigational or marketed) within 1 month of Screening * Prior arthroscopic or open surgery of the index knee within 12 months of Screening * Planned/anticipated surgery of the index knee during the study period * History of or active malignancy, with the exception of resected basal cell carcinoma, squamous cell carcinoma of the skin, or resected cervical atypia or carcinoma in situ within 5 years * Insulin-dependent diabetes * History of or active Cushing's syndrome * Any other clinically significant acute or chronic medical conditions (e.g., uncontrolled diabetes) * Skin breakdown at the knee where the injection would take place * Women of child-bearing potential not using effective contraception or who are pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 24-hour Weighted Mean Serum Cortisol | Days 1-2, Days 14-15 (Week 2) and Days 42-43 (Week 6) | The primary pharmacodynamic endpoint was change from baseline (pre-dose) to Day 1-2, Day 14-15 (Week 2) and Day 42-43 (Week 6) in 24-hour weighted mean serum cortisol. This is defined as AUC over the 0-24 hour measurement period divided by 24 |
| Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 1 (1, 2, 4, 6, 8, 12 and 24 hours post dose) and Days 3, 4, 5, 8, 15, 22, 29, 36 and 43 | Concentrations below the limit of quantification of 50 pg/mL were treated as 0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 24-hour Urinary Free Cortisol Excretion | Baseline to Days 1-2, Baseline to Days 14-15 (Week 2) and Baseline to Days 42-43 (Week 6) | — |
| Total 24-hour Urinary Free Cortisol Excretion | Days 1-2, Days 14-15 (Week 2) and Days 42-43 (Week 6) | — |
| Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Baseline to Days 2, 3, 4, 5, 8, 14, 15, 22, 29, 36, 42 and 43 | Least square mean difference against TCA IR 40 mg |
Countries
Australia
Participant flow
Recruitment details
This study took place at 2 centers, both located in Australia. Enrollment for this study took approximately 1.5 months.
Pre-assignment details
Subjects were screened for eligibility within 14 days of being randomized
Participants by arm
| Arm | Count |
|---|---|
| FX006 10mg Single 3 mL IA injection | 5 |
| FX006 40mg Single 3 mL IA injection | 7 |
| FX006 60 mg Single 3 mL IA injection | 7 |
| TCA IR (40 mg) Single 1 mL IA injection | 5 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | FX006 10mg | FX006 40mg | FX006 60 mg | TCA IR (40 mg) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 63.2 years | 59.3 years | 64.9 years | 63 years | 62.5 years |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 3 Participants | 3 Participants | 16 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 4 Participants | 2 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 7 | 0 / 7 | 0 / 5 |
| other Total, other adverse events | 4 / 5 | 7 / 7 | 6 / 7 | 5 / 5 |
| serious Total, serious adverse events | 0 / 5 | 0 / 7 | 0 / 7 | 0 / 5 |
Outcome results
Primary
Change From Baseline in 24-hour Weighted Mean Serum Cortisol
The primary pharmacodynamic endpoint was change from baseline (pre-dose) to Day 1-2, Day 14-15 (Week 2) and Day 42-43 (Week 6) in 24-hour weighted mean serum cortisol. This is defined as AUC over the 0-24 hour measurement period divided by 24
Time frame: Days 1-2, Days 14-15 (Week 2) and Days 42-43 (Week 6)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| FX006 10mg | Change From Baseline in 24-hour Weighted Mean Serum Cortisol | Change from BL to Days 1 to 2 | -7.7 weighted mean serum cortisol (nmol/L) |
| FX006 10mg | Change From Baseline in 24-hour Weighted Mean Serum Cortisol | Change in BL to Days 42 to 43 | -9.0 weighted mean serum cortisol (nmol/L) |
| FX006 10mg | Change From Baseline in 24-hour Weighted Mean Serum Cortisol | Change from BL to Days 14 to 15 | -11.1 weighted mean serum cortisol (nmol/L) |
| FX006 40mg | Change From Baseline in 24-hour Weighted Mean Serum Cortisol | Change from BL to Days 1 to 2 | -42.7 weighted mean serum cortisol (nmol/L) |
| FX006 40mg | Change From Baseline in 24-hour Weighted Mean Serum Cortisol | Change in BL to Days 42 to 43 | -18.0 weighted mean serum cortisol (nmol/L) |
| FX006 40mg | Change From Baseline in 24-hour Weighted Mean Serum Cortisol | Change from BL to Days 14 to 15 | -33.4 weighted mean serum cortisol (nmol/L) |
| FX006 60 mg | Change From Baseline in 24-hour Weighted Mean Serum Cortisol | Change from BL to Days 14 to 15 | -49.5 weighted mean serum cortisol (nmol/L) |
| FX006 60 mg | Change From Baseline in 24-hour Weighted Mean Serum Cortisol | Change from BL to Days 1 to 2 | -62.2 weighted mean serum cortisol (nmol/L) |
| FX006 60 mg | Change From Baseline in 24-hour Weighted Mean Serum Cortisol | Change in BL to Days 42 to 43 | -11.8 weighted mean serum cortisol (nmol/L) |
| TCA IR 40 mg | Change From Baseline in 24-hour Weighted Mean Serum Cortisol | Change from BL to Days 1 to 2 | -59.0 weighted mean serum cortisol (nmol/L) |
| TCA IR 40 mg | Change From Baseline in 24-hour Weighted Mean Serum Cortisol | Change in BL to Days 42 to 43 | -4.8 weighted mean serum cortisol (nmol/L) |
| TCA IR 40 mg | Change From Baseline in 24-hour Weighted Mean Serum Cortisol | Change from BL to Days 14 to 15 | -19.7 weighted mean serum cortisol (nmol/L) |
Primary
Characterize the Pharmacokinetic Profile of FX006 and TCA IR
Concentrations below the limit of quantification of 50 pg/mL were treated as 0.
Time frame: Day 1 (1, 2, 4, 6, 8, 12 and 24 hours post dose) and Days 3, 4, 5, 8, 15, 22, 29, 36 and 43
Population: PK population was to include all patients who received study drug and had at least one measurable concentration
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| FX006 10mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 22 (504 hrs post dose) | 0.000 pg/mL | Standard Deviation 0 |
| FX006 10mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 43 (1008 hrs post dose) | 0.000 pg/mL | Standard Deviation 0 |
| FX006 10mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 8 hours postdose | 249.298 pg/mL | Standard Deviation 0.464 |
| FX006 10mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 1 hour postdose | 140.941 pg/mL | Standard Deviation 0.4767 |
| FX006 10mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 2 hours postdose | 226.058 pg/mL | Standard Deviation 0.2204 |
| FX006 10mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 6 hours postdose | 261.231 pg/mL | Standard Deviation 0.4108 |
| FX006 10mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 36 (840 hrs post dose) | 0.000 pg/mL | Standard Deviation 0 |
| FX006 10mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 29 (672 hrs post dose) | 0.000 pg/mL | Standard Deviation 0 |
| FX006 10mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 15 (336 hrs post dose) | 113.002 pg/mL | Standard Deviation 0.5244 |
| FX006 10mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 2 (24 hrs post dose) | 242.764 pg/mL | Standard Deviation 0.4037 |
| FX006 10mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 4 hours postdose | 280.406 pg/mL | Standard Deviation 0.3637 |
| FX006 10mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 8 (168 hrs post dose) | 185.257 pg/mL | Standard Deviation 0.5638 |
| FX006 10mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 4 (72 hrs post dose) | 224.987 pg/mL | Standard Deviation 0.4904 |
| FX006 10mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 3 (48 hrs post dose) | 233.138 pg/mL | Standard Deviation 0.3999 |
| FX006 10mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 5 (96 hrs post dose) | 242.533 pg/mL | Standard Deviation 0.3787 |
| FX006 10mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 12 hours postdose | 230.506 pg/mL | Standard Deviation 0.5331 |
| FX006 40mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 6 hours postdose | 814.647 pg/mL | Standard Deviation 0.7131 |
| FX006 40mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 2 hours postdose | 779.819 pg/mL | Standard Deviation 0.6778 |
| FX006 40mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 4 hours postdose | 860.476 pg/mL | Standard Deviation 0.7088 |
| FX006 40mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 12 hours postdose | 691.962 pg/mL | Standard Deviation 0.7456 |
| FX006 40mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 2 (24 hrs post dose) | 763.568 pg/mL | Standard Deviation 0.7423 |
| FX006 40mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 1 hour postdose | 638.447 pg/mL | Standard Deviation 0.6312 |
| FX006 40mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 8 hours postdose | 748.962 pg/mL | Standard Deviation 0.7898 |
| FX006 40mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 3 (48 hrs post dose) | 743.344 pg/mL | Standard Deviation 0.7583 |
| FX006 40mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 4 (72 hrs post dose) | 675.086 pg/mL | Standard Deviation 0.693 |
| FX006 40mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 5 (96 hrs post dose) | 690.857 pg/mL | Standard Deviation 0.7292 |
| FX006 40mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 8 (168 hrs post dose) | 586.977 pg/mL | Standard Deviation 0.7574 |
| FX006 40mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 15 (336 hrs post dose) | 365.970 pg/mL | Standard Deviation 0.7325 |
| FX006 40mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 22 (504 hrs post dose) | 238.529 pg/mL | Standard Deviation 0.7026 |
| FX006 40mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 29 (672 hrs post dose) | 189.422 pg/mL | Standard Deviation 0.6089 |
| FX006 40mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 36 (840 hrs post dose) | 0.000 pg/mL | Standard Deviation 0 |
| FX006 40mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 43 (1008 hrs post dose) | 138.660 pg/mL | Standard Deviation 0.6253 |
| FX006 60 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 15 (336 hrs post dose) | 718.787 pg/mL | Standard Deviation 0.5587 |
| FX006 60 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 2 hours postdose | 1164.013 pg/mL | Standard Deviation 0.6772 |
| FX006 60 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 22 (504 hrs post dose) | 521.843 pg/mL | Standard Deviation 0.4563 |
| FX006 60 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 3 (48 hrs post dose) | 1294.042 pg/mL | Standard Deviation 0.7645 |
| FX006 60 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 12 hours postdose | 1127.476 pg/mL | Standard Deviation 0.7841 |
| FX006 60 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 2 (24 hrs post dose) | 1309.260 pg/mL | Standard Deviation 0.5869 |
| FX006 60 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 36 (840 hrs post dose) | 246.176 pg/mL | Standard Deviation 0.3844 |
| FX006 60 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 4 hours postdose | 1251.776 pg/mL | Standard Deviation 0.703 |
| FX006 60 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 8 (168 hrs post dose) | 1070.823 pg/mL | Standard Deviation 0.6322 |
| FX006 60 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 6 hours postdose | 1182.925 pg/mL | Standard Deviation 0.6952 |
| FX006 60 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 4 (72 hrs post dose) | 1270.953 pg/mL | Standard Deviation 0.7088 |
| FX006 60 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 1 hour postdose | 862.574 pg/mL | Standard Deviation 0.6823 |
| FX006 60 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 29 (672 hrs post dose) | 369.683 pg/mL | Standard Deviation 0.4589 |
| FX006 60 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 8 hours postdose | 1227.658 pg/mL | Standard Deviation 0.6245 |
| FX006 60 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 43 (1008 hrs post dose) | 187.435 pg/mL | Standard Deviation 0.3924 |
| FX006 60 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 5 (96 hrs post dose) | 1252.021 pg/mL | Standard Deviation 0.7097 |
| TCA IR 40 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 15 (336 hrs post dose) | 0.000 pg/mL | Standard Deviation 0 |
| TCA IR 40 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 29 (672 hrs post dose) | 0.000 pg/mL | Standard Deviation 0 |
| TCA IR 40 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 3 (48 hrs post dose) | 2371.778 pg/mL | Standard Deviation 1.1844 |
| TCA IR 40 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 2 (24 hrs post dose) | 5421.894 pg/mL | Standard Deviation 1.5196 |
| TCA IR 40 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 2 hours postdose | 14243.604 pg/mL | Standard Deviation 1.5643 |
| TCA IR 40 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 5 (96 hrs post dose) | 822.243 pg/mL | Standard Deviation 0.6002 |
| TCA IR 40 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 8 (168 hrs post dose) | 235.938 pg/mL | Standard Deviation 1.0814 |
| TCA IR 40 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 12 hours postdose | 10112.863 pg/mL | Standard Deviation 1.6684 |
| TCA IR 40 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 36 (840 hrs post dose) | 0.000 pg/mL | Standard Deviation 0 |
| TCA IR 40 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 22 (504 hrs post dose) | 0.000 pg/mL | Standard Deviation 0 |
| TCA IR 40 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 43 (1008 hrs post dose) | 0.000 pg/mL | Standard Deviation 0 |
| TCA IR 40 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 4 hours postdose | 16282.659 pg/mL | Standard Deviation 1.7765 |
| TCA IR 40 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 1 hour postdose | 12268.835 pg/mL | Standard Deviation 1.4681 |
| TCA IR 40 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 6 hours postdose | 14560.886 pg/mL | Standard Deviation 1.7754 |
| TCA IR 40 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | 8 hours postdose | 13543.427 pg/mL | Standard Deviation 1.7347 |
| TCA IR 40 mg | Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Day 4 (72 hrs post dose) | 1310.061 pg/mL | Standard Deviation 0.8301 |
Secondary
Change From Baseline in 24-hour Urinary Free Cortisol Excretion
Time frame: Baseline to Days 1-2, Baseline to Days 14-15 (Week 2) and Baseline to Days 42-43 (Week 6)
Population: Full Analysis Set (FAS) includes all observations from all patients who received a dose of study drug and provided a baseline observation and at least one post baseline observation.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| FX006 10mg | Change From Baseline in 24-hour Urinary Free Cortisol Excretion | Day 1 to 2 | 47.9 nmol/24h |
| FX006 10mg | Change From Baseline in 24-hour Urinary Free Cortisol Excretion | Day 42 to 43 | 7.7 nmol/24h |
| FX006 10mg | Change From Baseline in 24-hour Urinary Free Cortisol Excretion | Day 14 to 15 | 13.0 nmol/24h |
| FX006 40mg | Change From Baseline in 24-hour Urinary Free Cortisol Excretion | Day 1 to 2 | -43.8 nmol/24h |
| FX006 40mg | Change From Baseline in 24-hour Urinary Free Cortisol Excretion | Day 42 to 43 | -38.3 nmol/24h |
| FX006 40mg | Change From Baseline in 24-hour Urinary Free Cortisol Excretion | Day 14 to 15 | -42.4 nmol/24h |
| FX006 60 mg | Change From Baseline in 24-hour Urinary Free Cortisol Excretion | Day 14 to 15 | -59.0 nmol/24h |
| FX006 60 mg | Change From Baseline in 24-hour Urinary Free Cortisol Excretion | Day 1 to 2 | -50.1 nmol/24h |
| FX006 60 mg | Change From Baseline in 24-hour Urinary Free Cortisol Excretion | Day 42 to 43 | -13.1 nmol/24h |
| TCA IR 40 mg | Change From Baseline in 24-hour Urinary Free Cortisol Excretion | Day 1 to 2 | -58.5 nmol/24h |
| TCA IR 40 mg | Change From Baseline in 24-hour Urinary Free Cortisol Excretion | Day 42 to 43 | -21.3 nmol/24h |
| TCA IR 40 mg | Change From Baseline in 24-hour Urinary Free Cortisol Excretion | Day 14 to 15 | -14.7 nmol/24h |
Secondary
Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol
Least square mean difference against TCA IR 40 mg
Time frame: Baseline to Days 2, 3, 4, 5, 8, 14, 15, 22, 29, 36, 42 and 43
Population: The full analysis set will include all observations from all patients who received any dose of FX006 and provide a baseline observation and at least one post baseline observation.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| FX006 10mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 8 | -29.8 nmol/L |
| FX006 10mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 29 | -4.5 nmol/L |
| FX006 10mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 42 | -18.3 nmol/L |
| FX006 10mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 4 | -13.9 nmol/L |
| FX006 10mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 2 | -30.2 nmol/L |
| FX006 10mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 36 | -6.4 nmol/L |
| FX006 10mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 22 | 3.3 nmol/L |
| FX006 10mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 15 | -24.4 nmol/L |
| FX006 10mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 5 | -12.4 nmol/L |
| FX006 10mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 3 | -24.9 nmol/L |
| FX006 10mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 43 | -22.1 nmol/L |
| FX006 10mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 14 | -7.6 nmol/L |
| FX006 40mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 42 | -27.0 nmol/L |
| FX006 40mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 3 | -40.8 nmol/L |
| FX006 40mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 4 | -37.1 nmol/L |
| FX006 40mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 5 | -35.1 nmol/L |
| FX006 40mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 22 | -28.5 nmol/L |
| FX006 40mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 29 | -21.1 nmol/L |
| FX006 40mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 36 | -19.5 nmol/L |
| FX006 40mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 8 | -37.4 nmol/L |
| FX006 40mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 14 | -35.5 nmol/L |
| FX006 40mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 15 | -28.1 nmol/L |
| FX006 40mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 2 | -42.3 nmol/L |
| FX006 40mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 43 | -14.9 nmol/L |
| FX006 60 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 22 | -14.4 nmol/L |
| FX006 60 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 15 | -46.4 nmol/L |
| FX006 60 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 2 | -78.2 nmol/L |
| FX006 60 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 4 | -77.2 nmol/L |
| FX006 60 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 14 | -40.4 nmol/L |
| FX006 60 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 43 | -13.4 nmol/L |
| FX006 60 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 42 | -19.1 nmol/L |
| FX006 60 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 36 | -3.0 nmol/L |
| FX006 60 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 8 | -61.7 nmol/L |
| FX006 60 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 5 | -73.0 nmol/L |
| FX006 60 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 3 | -80.2 nmol/L |
| FX006 60 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 29 | -6.3 nmol/L |
| TCA IR 40 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 3 | -86.2 nmol/L |
| TCA IR 40 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 5 | -49.8 nmol/L |
| TCA IR 40 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 22 | -11.3 nmol/L |
| TCA IR 40 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 42 | -21.4 nmol/L |
| TCA IR 40 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 8 | -8.6 nmol/L |
| TCA IR 40 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 14 | -27.3 nmol/L |
| TCA IR 40 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 4 | -73.1 nmol/L |
| TCA IR 40 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 43 | 3.0 nmol/L |
| TCA IR 40 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 15 | -8.3 nmol/L |
| TCA IR 40 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 2 | -85.4 nmol/L |
| TCA IR 40 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 36 | 11.7 nmol/L |
| TCA IR 40 mg | Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol | Day 29 | 0.8 nmol/L |
Secondary
Total 24-hour Urinary Free Cortisol Excretion
Time frame: Days 1-2, Days 14-15 (Week 2) and Days 42-43 (Week 6)
Population: FAS includes all observations from all patients who received a dose of study drug and provided a baseline observation and at least one post baseline observation.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| FX006 10mg | Total 24-hour Urinary Free Cortisol Excretion | Day 1 to 2 | 75.66 nmol/24h | Standard Deviation 1.112 |
| FX006 10mg | Total 24-hour Urinary Free Cortisol Excretion | Day 42 to 43 | 55.74 nmol/24h | Standard Deviation 0.715 |
| FX006 10mg | Total 24-hour Urinary Free Cortisol Excretion | Day 14 to 15 | 57.14 nmol/24h | Standard Deviation 0.842 |
| FX006 40mg | Total 24-hour Urinary Free Cortisol Excretion | Day 1 to 2 | 29.94 nmol/24h | Standard Deviation 0.77 |
| FX006 40mg | Total 24-hour Urinary Free Cortisol Excretion | Day 42 to 43 | 34.62 nmol/24h | Standard Deviation 0.557 |
| FX006 40mg | Total 24-hour Urinary Free Cortisol Excretion | Day 14 to 15 | 30.91 nmol/24h | Standard Deviation 0.59 |
| FX006 60 mg | Total 24-hour Urinary Free Cortisol Excretion | Day 14 to 15 | 26.46 nmol/24h | Standard Deviation 0.925 |
| FX006 60 mg | Total 24-hour Urinary Free Cortisol Excretion | Day 1 to 2 | 29.36 nmol/24h | Standard Deviation 0.49 |
| FX006 60 mg | Total 24-hour Urinary Free Cortisol Excretion | Day 42 to 43 | 51.16 nmol/24h | Standard Deviation 0.499 |
| TCA IR 40 mg | Total 24-hour Urinary Free Cortisol Excretion | Day 1 to 2 | 18.77 nmol/24h | Standard Deviation 0.289 |
| TCA IR 40 mg | Total 24-hour Urinary Free Cortisol Excretion | Day 42 to 43 | 36.38 nmol/24h | Standard Deviation 0.626 |
| TCA IR 40 mg | Total 24-hour Urinary Free Cortisol Excretion | Day 14 to 15 | 36.22 nmol/24h | Standard Deviation 0.962 |