Safety and Efficacy of LCI699 in Cushing's Disease Patients
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01331239
Collaborator
(none)
31
10
3
103
3.1
0
Study Details
Study Description
Brief Summary
This exploratory study is a proof of concept study to determine whether LCI699 can safely reduce the level of urinary free cortisol in patients with Cushing's disease.
In addition, this study evaluated the long term efficacy and safety of LCI699 including an additional 12 week of treatment followed by a 12 month long term optional extension.
A second extension provided patients who were clinically benefitting from LCI699 an opportunity to continue to have access to the drug until LCI699 was commercially available and reimbursed or through the availability of a local access program.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
The Primary objective of this study was to assess the effect of 10-week treatment osilodrostat on 24 hour urine free cortisol (UFC) in patients with Cushing's disease.
The study consisted of a screening period of up to 60 days (to allow an adequate washout period for any medications that modified cortisol levels), a 10-14-day baseline period, a 10-week sequential dose escalation treatment period and a 14-day washout period followed by a Study Completion evaluation approximately 14 days after the last drug administration. Twelve patients were recruited and completed Part l of the study.
Eligible patients were dosed at 2 mg b.i.d for the first two weeks, the dose could then be increased every two weeks as necessary (to doses of 5, 10, 20 and 50 mg b.i.d). If at anytime, the subject's UFC was < Upper Limit of Normal (ULN), dose escalation was halted and the subject remained on the current, efficacious dose through Week 10, with continued monitoring of UFC responses every 2 weeks to allow continued dose adjustments if necessary. If at any time the subject experienced side effects which were either intolerable or met dose adjustment criteria, the prescribed dose was adjusted.
The primary endpoint (UFC ≤ ULN or ≥50% decrease at Day 70) was achieved by all patients. Subsequently, in order to confirm these observations, protocol was amended (Protocol amendment 4) and new patients were enrolled and investigated for a longer treatment period.
Following Protocol amendment 4, the study design was modified to include patients in Part II of the study for evaluating the long-term efficacy and safety of osilodrostat treatment for 22 weeks. Nineteen patients (15 who were treated in the expansion cohort in Part ll and 4 who participated in Part l) with Cushing's disease were enrolled as part of the Expansion cohort in Part II of the study. The 12 patients who had entered the study in Part I, were allowed to re-enter the study as the Core proof of concept (PoC) Follow-up cohort. At Day 70 ± 2 days (Week 10), all patients (both patients entering for the first time and those reentering the study) entered the 12-week assessment period. At Day 154, patients completed the End of Treatment-Core visit.
On Day 154 (Week 22), patients had the option to enter the 12-month extension phase (long-term extension 1). On Day 490, patients who continued in the study had the option to enter a second long term extension phase (extension-2) at the Investigator's discretion, provided they did not meet any of the study discontinuation criteria.
Study Design
Study Type:
Interventional
Actual Enrollment
:
31 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Proof of Concept, Open-label, Forced Titration, Multi-center Study to Assess the Safety/Tolerability and Efficacy of 10-weeks Treatment of LCI699 in Patients With Cushing's Disease
Actual Study Start Date
:
Mar 23, 2011
Actual Primary Completion Date
:
Oct 22, 2019
Actual Study Completion Date
:
Oct 22, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part l: Core cohort Participants took an ascending dose of LCI699 (osilodrostat) from 2mg bid or 5 mg bid, up to 30 mg bid and participated in Part I of this study. 4 patients in this cohort moved to Part II of the study |
Drug: LCI699
Osilodrostat 1 mg and 5 mg capsules, was prepared by Novartis and supplied to the Investigator. The capsule formulation of osilodrostat was later changed to tablets and this change was implemented in the study with Protocol amendment 6. Osilodrostat was open labeled 1 mg, 5 mg, 10 mg and 20 mg tablets.
Other Names:
|
| Experimental: Part II Core: Expansion cohort Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part II Core Expansion of this study. These patients were all newly enrolled into the phase II part of the study |
Drug: LCI699
Osilodrostat 1 mg and 5 mg capsules, was prepared by Novartis and supplied to the Investigator. The capsule formulation of osilodrostat was later changed to tablets and this change was implemented in the study with Protocol amendment 6. Osilodrostat was open labeled 1 mg, 5 mg, 10 mg and 20 mg tablets.
Other Names:
|
| Experimental: Part II Core: Follow-up cohort Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part II Core Follow-up of this study. These patients were patients who transferred from Part I Core phase of the study |
Drug: LCI699
Osilodrostat 1 mg and 5 mg capsules, was prepared by Novartis and supplied to the Investigator. The capsule formulation of osilodrostat was later changed to tablets and this change was implemented in the study with Protocol amendment 6. Osilodrostat was open labeled 1 mg, 5 mg, 10 mg and 20 mg tablets.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Responders to LCI699 Based on the Change in Mean Urinary Free Cortisol (UFC) From Baseline to Week 10 [10 weeks]
A patient was considered to be a responder if his/her mean UFC level from the three 24-hour urine samples collected at Week 10 was ≤ Upper Limit of Normal (ULN), as defined by the local laboratories, or represented a ≥50% decrease from baseline. Patients who discontinued for a disease or treatment related reason (e.g. death, adverse event, clinical disease progression etc.), or whose mean Week 10 24-hour UFC levels were higher than the normal limit and experienced <50% decrease in UFC were classified as non-responders.
Secondary Outcome Measures
- Actual Change From Baseline (BL) in Steroid Hormones of Hypothalamic-Pituitary-Adrenal (HPA)-Axis: 11- Deoxycorticosterone (Overall) [baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88]
Change in Deoxycorticosterone over time.
- Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: 11-Deoxycortisol (Overall) [baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88]
Change in Deoxycortisol over time.
- Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Aldosterone, Thyroxine, Free (T4) [baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88]
Change in aldosterone & thyroxine, free over time.
- Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Estradiol (Female) [baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88]
Change in Estradiol in females over time.
- Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Estradiol (Male) [baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88]
Change in Estradiol in males over time.
- Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Follicle Stimulation Hormone (FSH) (Female) [baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88]
Change in FSH in females over time.
- Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Follicle Stimulation Hormone (Male) [baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88]
Change in FSH in males over time.
- Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Renin, Insulin, Thyrotropin [baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88]
Change in Renin, Insulin & Thyrotropin over time.
- Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Insulin-like Growth Factor-1 [baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88]
Change in Insulin-like Growth Factor-1 over time.
- Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Luteinising Hormone (LH) (Female) [baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88]
Change in LH in females over time.
- Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: LH (Male) [baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88]
Change in LH in males over time.
- Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Testosterone (Female) [baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88]
Change in Testosterone in females over time.
- Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Testosterone (Male) [baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88]
Change in Testosterone in males over time.
- Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Fasting Glucose [Baseline, Week 22, Week 70, Last observed value, up to Month 88]
Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline.
- Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Hemoglobin A1C (HbA1C) (Glycosylated Hemoglobin) [Baseline, Week 22, Week 70, Last observed value, up to Month 88]
Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline.
- Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Cholesterol, LDL Cholesterol, HDL Cholesterol, Triglycerides [Baseline, Week 22, Week 70, Last observed value, up to Month 88]
Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline.
- Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Sitting Diastolic Blood Pressure (DBP), Sitting Systolic Blood Pressure (SBP) [Baseline, Week 22, Week 70, Last observed value, up to Month 88]
Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline.
- Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Weight [Baseline, Week 22, Week 70, Last observed value, up to Month 88]
Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline.
- Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Body Mass Index (BMI) [Baseline, Week 22, Week 70, Last observed value, up to Month 88]
Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline.
- Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Quantitative Insulin Sensitivity Check Index (QUICKI) [Baseline, Week 22, Week 70, Last observed value, up to Month 88]
Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline. QUICKI is the quantitative insulin sensitivity check index and is derived using the inverse of the sum of algorithms (base 10) of the fasting insulin and fasting glucose: 1/(log(fasting insulin mU/mL)+log(fasting glucose mg/dL)). Values typically associated with the QUICKI calculation for insulin resistance in humans fall broadly within a range between 0.45 for unusually healthy individuals and 0.30 in diabetics. So lower numbers reflect greater insulin resistance.
- Pharmacokinetics (PK) Parameters: Area Under Curve (AUC)0-6h ss, AUC0-12h ss [pre-dose (0 hour), 1, 1.5, 2, 4 and 6 hours post AM dose for escalation dose or pre-dose (trough) for maintained dose]
Trough PK concentrations and PK profiles at steady-state were collected. The AUC from time 0 to 12 h post dose at steady state, calculated by using the predose concentration (Ctrough,ss) as the 12 h concentration, assuming steady-state has been reached.
- PK Parameters: Cmax ss, Ctrough ss [pre-dose (0 hour), 1, 1.5, 2, 4 and 6 hours post AM dose for escalation dose or pre-dose (trough) for maintained dose]
Trough PK concentrations and PK profiles at steady-state were collected.
- PK Parameters: Tmax ss, [pre-dose (0 hour), 1, 1.5, 2, 4 and 6 hours post AM dose for escalation dose or pre-dose (trough) for maintained dose]
Trough PK concentrations and PK profiles at steady-state were collected.
- PK Parameters: T1/2 ss, [pre-dose (0 hour), 1, 1.5, 2, 4 and 6 hours post AM dose for escalation dose or pre-dose (trough) for maintained dose]
Trough PK concentrations and PK profiles at steady-state were collected.
- Percentage of Participants Who Were Responders on 24-hour Urine Free Cortisol (UFC) at Week 22 [Week 22]
A patient was considered to be a responder if his/her mean UFC level from the three 24-hour urine samples collected at Week 22 was ≤ ULN (as defined by the local laboratories) or represented a ≥50% decrease from baseline. Participants with controlled or partially controlled UFC were defined as: Controlled UFC: mean UFC level <= upper limit of normal (ULN). Partially controlled UFC: mean UFC level > ULN but with >= 50% reduction from baseline.
- Number of Participants With Escape [approx. 7 years]
Escape is defined as loss of UFC control (i.e. UFC > ULN) on at least 2 consecutive visits at the highest tolerated dose after previously attaining UFC normalization)
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Patients with a confirmed diagnosis of Cushing's Disease (persistent or recurrent) as evidenced by increased 24-hour urine free cortisol (UFC), normal or increased morning plasma Adrenocorticotropic Hormone (ACTH), and pituitary origin of excess ACTH.
-
Patients with de novo Cushing's disease can be included only if they are not considered candidate for surgery
Exclusion Criteria:
-
Patients treated with mitotane 6 months prior to Visit 1
-
Patients with compression of the optic chiasm
-
Patients with a known inherited syndrome as the cause for hormone over secretion
-
Patients with Cushing's syndrome due to ectopic ACTH secretion or adrenal Cushing's syndrome
-
Patients with pseudo-Cushing's syndrome
-
Patients who are not biochemically euthyroid
-
Diabetic patients with poorly controlled diabetes (HbA1c >9%)
-
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 1 week after completion of dosing.
-
Patients who have received pituitary irradiation within five years prior to Visit 1.
-
Patients with risk factors for QTc prolongation or Torsade de Pointes.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Northwestern University Endo, Metabolism and Molecular | Chicago | Illinois | United States | 60611-3308 |
| 2 | Massachusetts General Hospital Neuroendocrine Unit | Boston | Massachusetts | United States | 02114 |
| 3 | Cleveland Clinic Foundation | Cleveland | Ohio | United States | 44195 |
| 4 | Oregon Health and Science University SC | Portland | Oregon | United States | 97239-3098 |
| 5 | Novartis Investigative Site | Le Kremlin Bicetre | France | 94275 | |
| 6 | Novartis Investigative Site | Paris | France | 75014 | |
| 7 | Novartis Investigative Site | Ancona | Italy | L60020 | |
| 8 | Novartis Investigative Site | Napoli | Italy | 80131 | |
| 9 | Novartis Investigative Site | Sapporo city | Hokkaido | Japan | 060 8648 |
| 10 | Novartis Investigative Site | Chiba | Japan | 260 8677 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01331239
Other Study ID Numbers:
- CLCI699C2201
- 2010-022403-22
First Posted:
Apr 8, 2011
Last Update Posted:
Jan 22, 2021
Last Verified:
Jan 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | 31 were enrolled in the study: 12 in Part l and 19 in Part ll Core. Four of the participants in the Part II Core were previously enrolled in the Part I Core. That is, 4 participants who were included in Part 1 as well as in Part 2, re-enrolled in the study in part 2 (i.e., they completed the informed consent process again in Part 2, and were considered re-enrolled, after originally enrolling in part 1). |
|---|---|
| Pre-assignment Detail | For overall study: 27 patients were planned; For Part l of the study, 12 - 15 patients were planned to be enrolled. For Part ll Core 19 patients were planned to be enrolled. |
| Arm/Group Title | Part l: Core Cohort | Part II Core: Expansion Cohort | Part ll Core: Follow-up Cohort |
|---|---|---|---|
| Arm/Group Description | Participants took an ascending dose of LCI699 (osilodrostat) from 2mg bid or 5 mg bid, up to 30 mg bid and participated in Part l of this study. 4 patients in this cohort moved to Part II of the study | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Period Title: Part I: Core Study | |||
| STARTED | 12 | 0 | 0 |
| COMPLETED | 12 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 |
| Period Title: Part I: Core Study | |||
| STARTED | 0 | 15 | 4 |
| COMPLETED | 0 | 7 | 3 |
| NOT COMPLETED | 0 | 8 | 1 |
Baseline Characteristics
| Arm/Group Title | Part l: Core Cohort | Part II Core: Expansion Cohort | Total |
|---|---|---|---|
| Arm/Group Description | Participants took an ascending dose of LCI699 (osilodrostat) from 2mg bid or 5 mg bid, up to 30 mg bid and participated in Part l of this study. 4 patients in this cohort moved to Part II of the study | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Total of all reporting groups |
| Overall Participants | 12 | 15 | 27 |
| Age, Customized (Number) [Number] | |||
| <65 years |
12
100%
|
15
100%
|
27
100%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
8
66.7%
|
11
73.3%
|
19
70.4%
|
| Male |
4
33.3%
|
4
26.7%
|
8
29.6%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| White |
12
100%
|
11
73.3%
|
23
85.2%
|
| Black or African American |
0
0%
|
3
20%
|
3
11.1%
|
| Asian |
0
0%
|
1
6.7%
|
1
3.7%
|
Outcome Measures
| Title | Percentage of Responders to LCI699 Based on the Change in Mean Urinary Free Cortisol (UFC) From Baseline to Week 10 |
|---|---|
| Description | A patient was considered to be a responder if his/her mean UFC level from the three 24-hour urine samples collected at Week 10 was ≤ Upper Limit of Normal (ULN), as defined by the local laboratories, or represented a ≥50% decrease from baseline. Patients who discontinued for a disease or treatment related reason (e.g. death, adverse event, clinical disease progression etc.), or whose mean Week 10 24-hour UFC levels were higher than the normal limit and experienced <50% decrease in UFC were classified as non-responders. |
| Time Frame | 10 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary Analysis Set: All patients with evaluable UFC data (at least two 24 hour measurements for both baseline and Week 10) were included in the primary efficacy analysis set. Of the 12 patients enrolled to this arm, 9 of the 12 patients met this criteria. |
| Arm/Group Title | Part l: Core Cohort |
|---|---|
| Arm/Group Description | Participants took an ascending dose of LCI699 (osilodrostat) from 2mg bid or 5 mg bid, up to 30 mg bid and participated in Part l of this study. 4 patients in this cohort moved to Part II of the study |
| Measure Participants | 9 |
| Number [Percentage of participants] |
100.0
833.3%
|
| Title | Actual Change From Baseline (BL) in Steroid Hormones of Hypothalamic-Pituitary-Adrenal (HPA)-Axis: 11- Deoxycorticosterone (Overall) |
|---|---|
| Description | Change in Deoxycorticosterone over time. |
| Time Frame | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS): All patients in the Core proof of concept (PoC) follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. |
| Arm/Group Title | Part II Core: Expansion Cohort | Part ll Core: Follow-up Cohort |
|---|---|---|
| Arm/Group Description | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Measure Participants | 15 | 4 |
| BL: 11-Deoxycorticosterone |
292.8
(371.54)
|
188.0
(105.21)
|
| WK 22: 11-Deoxycorticosterone |
6957.8
(9627.77)
|
3670.0
(2734.34)
|
| WK 70: 11-Deoxycorticosterone |
2523.1
(1597.39)
|
1743.0
(1048.22)
|
| LOV: 11-Deoxycorticosterone |
1640.8
(2097.16)
|
1822.3
(1452.72)
|
| Title | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: 11-Deoxycortisol (Overall) |
|---|---|
| Description | Change in Deoxycortisol over time. |
| Time Frame | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. |
| Arm/Group Title | Part II Core: Expansion Cohort | Part ll Core: Follow-up Cohort |
|---|---|---|
| Arm/Group Description | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Measure Participants | 15 | 4 |
| BL: 11-Deoxycortisol |
4.21
(4.648)
|
5.48
(6.549)
|
| WK 22: 11-Deoxycortisol |
45.48
(44.880)
|
54.75
(60.676)
|
| WK 70: 11-Deoxycortisol |
15.32
(13.463)
|
9.03
(7.934)
|
| LOV: 11-Deoxycortisol |
8.60
(18.910)
|
11.83
(19.101)
|
| Title | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Aldosterone, Thyroxine, Free (T4) |
|---|---|
| Description | Change in aldosterone & thyroxine, free over time. |
| Time Frame | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. |
| Arm/Group Title | Part II Core: Expansion Cohort | Part ll Core: Follow-up Cohort |
|---|---|---|
| Arm/Group Description | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Measure Participants | 15 | 4 |
| BL: Aldosterone |
165.5
(255.07)
|
127.0
(177.04)
|
| WK 22: Aldosterone |
-151.1
(290.53)
|
-64.5
(247.93)
|
| WK 70: Aldosterone |
-101.9
(153.82)
|
-120.0
(182.11)
|
| LOV: Aldosterone |
-135.1
(258.36)
|
-99.5
(149.06)
|
| BL: Thyroxine, free |
14.02
(3.233)
|
18.40
(8.050)
|
| WK 22: Thyroxine, free |
-1.17
(3.254)
|
-3.63
(3.247)
|
| WK 70: Thyroxine, free |
0.46
(2.355)
|
-3.78
(7.951)
|
| LOV: Thyroxine, free |
1.69
(3.281)
|
-2.33
(5.324)
|
| Title | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Estradiol (Female) |
|---|---|
| Description | Change in Estradiol in females over time. |
| Time Frame | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. This analysis was on the female patients only. |
| Arm/Group Title | Part II Core: Expansion Cohort | Part ll Core: Follow-up Cohort |
|---|---|---|
| Arm/Group Description | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Measure Participants | 11 | 3 |
| BL: Female Estradiol |
209.60
(282.423)
|
307.23
(263.028)
|
| WK 22: Female Estradiol |
-42.19
(223.444)
|
-24.63
(234.288)
|
| WK 70: Female Estradiol |
10.55
(187.443)
|
-141.00
(376.080)
|
| LOV: Female Estradiol |
-114.24
(305.334)
|
666.93
(1108.794)
|
| Title | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Estradiol (Male) |
|---|---|
| Description | Change in Estradiol in males over time. |
| Time Frame | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. This analysis was on the male patients only. |
| Arm/Group Title | Part II Core: Expansion Cohort | Part ll Core: Follow-up Cohort |
|---|---|---|
| Arm/Group Description | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Measure Participants | 4 | 1 |
| BL: Male Estradiol |
55.00
(25.755)
|
77.10
(NA)
|
| WK 22: Male Estradiol |
35.00
(68.005)
|
18.30
(NA)
|
| WK 70: Male Estradiol |
-1.00
(16.523)
|
110.10
(NA)
|
| LOV: Male Estradiol |
2.50
(55.729)
|
-33.10
(NA)
|
| Title | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Follicle Stimulation Hormone (FSH) (Female) |
|---|---|
| Description | Change in FSH in females over time. |
| Time Frame | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. This analysis was on the female patients only. |
| Arm/Group Title | Part II Core: Expansion Cohort | Part ll Core: Follow-up Cohort |
|---|---|---|
| Arm/Group Description | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Measure Participants | 11 | 3 |
| BL: Female FSH |
9.09
(13.277)
|
2.43
(0.929)
|
| WK 22: Female FSH |
14.89
(28.673)
|
2.90
(2.476)
|
| WK 70: Female FSH |
3.58
(14.021)
|
3.20
(2.081)
|
| LOV: Female FSH |
15.41
(23.613)
|
3.70
(2.524)
|
| Title | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Follicle Stimulation Hormone (Male) |
|---|---|
| Description | Change in FSH in males over time. |
| Time Frame | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. This analysis was on the male patients only. |
| Arm/Group Title | Part II Core: Expansion Cohort | Part ll Core: Follow-up Cohort |
|---|---|---|
| Arm/Group Description | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Measure Participants | 4 | 1 |
| BL: Male FSH |
5.88
(3.241)
|
5.80
(NA)
|
| WK 22: Male FSH |
-1.20
(1.560)
|
-5.20
(NA)
|
| WK 70: Male FSH |
-1.80
(1.735)
|
-5.80
(NA)
|
| LOV: Male FSH |
-1.38
(5.660)
|
-2.90
(NA)
|
| Title | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Renin, Insulin, Thyrotropin |
|---|---|
| Description | Change in Renin, Insulin & Thyrotropin over time. |
| Time Frame | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. |
| Arm/Group Title | Part II Core: Expansion Cohort | Part ll Core: Follow-up Cohort |
|---|---|---|
| Arm/Group Description | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Measure Participants | 15 | 4 |
| BL: Renin |
23.706
(18.0642)
|
73.973
(102.338)
|
| WK 22: Renin |
45.899
(144.9575)
|
-16.838
(145.6609)
|
| WK 70: Renin |
70.051
(117.9931)
|
-55.638
(88.9155)
|
| LOV: Renin |
24.209
(52.0438)
|
-43.718
(70.5958)
|
| BL: Insulin |
25.61
(27.166)
|
22.38
(7.071)
|
| WK 22: Insulin |
-10.63
(20.247)
|
-8.58
(4.456)
|
| WK 70: Insulin |
-8.69
(24.132)
|
-12.53
(8.772)
|
| LOV: Insulin |
-8.11
(23.169)
|
-5.78
(11.771)
|
| BL: Thyrotropin |
0.659
(0.6827)
|
0.815
(0.8364)
|
| WK 22: Thyrotropin |
1.445
(2.3295)
|
0.280
(0.3118)
|
| WK 70: Thyrotropin |
2.387
(4.0991)
|
0.395
(0.4674)
|
| LOV: Thyrotropin |
1.244
(3.4627)
|
0.885
(0.5994)
|
| Title | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Insulin-like Growth Factor-1 |
|---|---|
| Description | Change in Insulin-like Growth Factor-1 over time. |
| Time Frame | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. |
| Arm/Group Title | Part II Core: Expansion Cohort | Part ll Core: Follow-up Cohort |
|---|---|---|
| Arm/Group Description | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Measure Participants | 15 | 4 |
| BL: Insulin-like Growth Factor-1 |
157.56
(109.044)
|
235.30
(110.249)
|
| WK 22: Insulin-like Growth Factor-1 |
-9.78
(67.387)
|
-35.20
(153.817)
|
| WK 70: Insulin-like Growth Factor-1 |
-41.23
(76.969)
|
-113.43
(86.529)
|
| LOV: Insulin-like Growth Factor-1 |
-56.76
(105.936)
|
-46.07
(62.155)
|
| Title | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Luteinising Hormone (LH) (Female) |
|---|---|
| Description | Change in LH in females over time. |
| Time Frame | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. This analysis was on the female patients only. |
| Arm/Group Title | Part II Core: Expansion Cohort | Part ll Core: Follow-up Cohort |
|---|---|---|
| Arm/Group Description | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Measure Participants | 11 | 3 |
| BL: Female LH |
2.78
(2.220)
|
1.00
(1.000)
|
| WK 22: Female LH |
7.45
(17.051)
|
4.40
(0.990)
|
| WK 70: Female LH |
7.47
(15.267)
|
2.63
(3.235)
|
| LOV: Female LH |
7.30
(10.885)
|
3.37
(2.060)
|
| Title | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: LH (Male) |
|---|---|
| Description | Change in LH in males over time. |
| Time Frame | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. This analysis was on the male patients only. |
| Arm/Group Title | Part II Core: Expansion Cohort | Part ll Core: Follow-up Cohort |
|---|---|---|
| Arm/Group Description | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Measure Participants | 4 | 1 |
| BL: Male LH |
2.48
(1.328)
|
5.90
(NA)
|
| WK 22: Male LH |
0.48
(1.081)
|
-5.70
(NA)
|
| WK 70: Male LH |
-0.53
(1.021)
|
-5.90
(NA)
|
| LOV: Male LH |
-0.05
(2.610)
|
-2.70
(NA)
|
| Title | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Testosterone (Female) |
|---|---|
| Description | Change in Testosterone in females over time. |
| Time Frame | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. This analysis was on the female patients only. |
| Arm/Group Title | Part II Core: Expansion Cohort | Part ll Core: Follow-up Cohort |
|---|---|---|
| Arm/Group Description | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Measure Participants | 11 | 3 |
| BL: Female Testosterone |
1.18
(0.820)
|
1.43
(0.404)
|
| WK 22: Female Testosterone |
1.85
(1.790)
|
5.27
(5.353)
|
| WK 70: Female Testosterone |
0.53
(1.409)
|
0.50
(1.400)
|
| LOV: Female Testosterone |
0.25
(1.532)
|
0.17
(1.266)
|
| Title | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Testosterone (Male) |
|---|---|
| Description | Change in Testosterone in males over time. |
| Time Frame | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. This analysis was on the male patients only. |
| Arm/Group Title | Part II Core: Expansion Cohort | Part ll Core: Follow-up Cohort |
|---|---|---|
| Arm/Group Description | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Measure Participants | 4 | 1 |
| BL: Male Testosterone |
7.53
(4.076)
|
7.10
(NA)
|
| WK 22: Male Testosterone |
6.55
(4.751)
|
2.40
(NA)
|
| WK 70: Male Testosterone |
5.17
(1.504)
|
32.60
(NA)
|
| LOV: Male Testosterone |
8.15
(7.859)
|
0.00
(NA)
|
| Title | Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Fasting Glucose |
|---|---|
| Description | Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline. |
| Time Frame | Baseline, Week 22, Week 70, Last observed value, up to Month 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. |
| Arm/Group Title | Part II Core: Expansion Cohort | Part ll Core: Follow-up Cohort |
|---|---|---|
| Arm/Group Description | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Measure Participants | 15 | 4 |
| BL |
108.1
(55.12)
|
96.3
(14.43)
|
| WK 22 |
-14.5
(32.45)
|
-16.3
(14.93)
|
| WK 70 |
-22.5
(36.87)
|
-20.8
(24.62)
|
| LOV |
-17.9
(35.99)
|
-13.8
(22.88)
|
| Title | Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Hemoglobin A1C (HbA1C) (Glycosylated Hemoglobin) |
|---|---|
| Description | Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline. |
| Time Frame | Baseline, Week 22, Week 70, Last observed value, up to Month 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. |
| Arm/Group Title | Part II Core: Expansion Cohort | Part II Core: Follow-up Cohort |
|---|---|---|
| Arm/Group Description | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Measure Participants | 15 | 4 |
| BL |
5.7
(0.77)
|
6.0
(0.61)
|
| WK 22 |
-0.1
(0.27)
|
-0.3
(0.28)
|
| WK 70 |
-0.1
(0.43)
|
-0.6
(0.74)
|
| LOV |
-0.1
(0.56)
|
-0.4
(0.49)
|
| Title | Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Cholesterol, LDL Cholesterol, HDL Cholesterol, Triglycerides |
|---|---|
| Description | Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline. |
| Time Frame | Baseline, Week 22, Week 70, Last observed value, up to Month 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. |
| Arm/Group Title | Part ll Core: Expansion Cohort | Part II Core: Follow-up Cohort |
|---|---|---|
| Arm/Group Description | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Measure Participants | 15 | 4 |
| BL Cholesterol |
5.2
(1.36)
|
5.7
(1.44)
|
| WK 22 Cholesterol |
-0.7
(1.58)
|
-0.5
(0.56)
|
| WK 70 Cholesterol |
-0.1
(1.35)
|
-1.2
(1.74)
|
| LOV Cholesterol |
0.5
(2.39)
|
1.5
(5.22)
|
| BL LDL Cholesterol |
3.0
(1.32)
|
4.8
(2.31)
|
| WK 22 LDL Cholesterol |
-0.3
(1.35)
|
-1.5
(1.98)
|
| WK 70 LDL Cholesterol |
0.0
(1.17)
|
-2.2
(2.11)
|
| LOV LDL Cholesterol |
0.3
(1.58)
|
-0.7
(1.83)
|
| BL HDL Cholesterol |
1.6
(0.39)
|
2.1
(1.85)
|
| WK 22 HDL Cholesterol |
-0.3
(0.32)
|
-0.9
(1.58)
|
| WK 70 HDL Cholesterol |
-0.3
(0.42)
|
-0.9
(1.60)
|
| LOV HDL Cholesterol |
0.1
(0.66)
|
-0.0
(0.49)
|
| BL Triglycerides |
1.5
(0.70)
|
1.4
(0.32)
|
| WK 22 Triglycerides |
-0.1
(0.42)
|
0.1
(0.49)
|
| WK 70 Triglycerides |
0.3
(0.76)
|
-0.2
(0.25)
|
| LOV Triglycerides |
0.1
(0.64)
|
-0.1
(0.54)
|
| Title | Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Sitting Diastolic Blood Pressure (DBP), Sitting Systolic Blood Pressure (SBP) |
|---|---|
| Description | Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline. |
| Time Frame | Baseline, Week 22, Week 70, Last observed value, up to Month 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. |
| Arm/Group Title | Part ll Core: Expansion Cohort | Part II Core: Follow-up Cohort |
|---|---|---|
| Arm/Group Description | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Measure Participants | 15 | 4 |
| BL DBP |
84.5
(7.01)
|
87.3
(4.21)
|
| WK 22 DPB |
0.8
(9.59)
|
2.6
(11.36)
|
| WK 70 DPB |
-3.4
(11.65)
|
-5.8
(12.14)
|
| LOV DPB |
-1.3
(9.23)
|
-3.2
(7.07)
|
| BL SBP |
133.2
(12.51)
|
130.3
(7.75)
|
| WK 22 SPB |
-4.0
(12.46)
|
8.8
(24.74)
|
| WK 70 SPB |
-9.5
(15.78)
|
-4.7
(26.09)
|
| LOV SPB |
-6.2
(16.50)
|
0.3
(20.60)
|
| Title | Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Weight |
|---|---|
| Description | Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline. |
| Time Frame | Baseline, Week 22, Week 70, Last observed value, up to Month 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. |
| Arm/Group Title | Part ll Core: Expansion Cohort | Part ll Core: Follow-up Cohort |
|---|---|---|
| Arm/Group Description | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Measure Participants | 15 | 4 |
| BL |
85.4
(23.52)
|
84.0
(23.32)
|
| WK 22 |
-2.1
(4.02)
|
0.6
(2.64)
|
| WK 70 |
-5.2
(4.56)
|
-3.2
(5.61)
|
| LOV |
-4.5
(6.68)
|
-4.4
(7.00)
|
| Title | Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Body Mass Index (BMI) |
|---|---|
| Description | Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline. |
| Time Frame | Baseline, Week 22, Week 70, Last observed value, up to Month 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. |
| Arm/Group Title | Part ll Core: Expansion Cohort | Part II Core: Follow-up Cohort |
|---|---|---|
| Arm/Group Description | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Measure Participants | 15 | 4 |
| BL |
30.6
(7.46)
|
31.3
(5.49)
|
| WK 22 |
-0.7
(1.42)
|
0.2
(1.09)
|
| WK 70 |
-1.9
(1.93)
|
-1.4
(2.25)
|
| LOV |
-1.6
(2.73)
|
-2.0
(2.73)
|
| Title | Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Quantitative Insulin Sensitivity Check Index (QUICKI) |
|---|---|
| Description | Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline. QUICKI is the quantitative insulin sensitivity check index and is derived using the inverse of the sum of algorithms (base 10) of the fasting insulin and fasting glucose: 1/(log(fasting insulin mU/mL)+log(fasting glucose mg/dL)). Values typically associated with the QUICKI calculation for insulin resistance in humans fall broadly within a range between 0.45 for unusually healthy individuals and 0.30 in diabetics. So lower numbers reflect greater insulin resistance. |
| Time Frame | Baseline, Week 22, Week 70, Last observed value, up to Month 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. |
| Arm/Group Title | Part ll Core: Expansion Cohort | Part II Core: Follow-up Cohort |
|---|---|---|
| Arm/Group Description | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Measure Participants | 15 | 4 |
| BL |
0.3
(0.03)
|
0.3
(0.02)
|
| WK 22 |
0.0
(0.02)
|
0.0
(0.01)
|
| WK 70 |
0.0
(0.03)
|
0.0
(0.06)
|
| LOV |
0.0
(0.04)
|
0.0
(0.04)
|
| Title | Pharmacokinetics (PK) Parameters: Area Under Curve (AUC)0-6h ss, AUC0-12h ss |
|---|---|
| Description | Trough PK concentrations and PK profiles at steady-state were collected. The AUC from time 0 to 12 h post dose at steady state, calculated by using the predose concentration (Ctrough,ss) as the 12 h concentration, assuming steady-state has been reached. |
| Time Frame | pre-dose (0 hour), 1, 1.5, 2, 4 and 6 hours post AM dose for escalation dose or pre-dose (trough) for maintained dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Analysis Set (PAS): all enrolled patients with at least 1 dose of study drug and at least 1 post-dose PK assessment after Protocol Amendment 4 or after re-entering the study. |
| Arm/Group Title | 2mg Bid | 5mg Bid | 10mg Bid | 20mg Bid | 30mg Bid |
|---|---|---|---|---|---|
| Arm/Group Description | Participants in the Expansion cohort who took 2mg of osilodrostat | Participants in the Expansion cohort who took 5mg of osilodrostat | Participants in the Expansion cohort who took 10mg of osilodrostat | Participants in the Expansion cohort who took 20mg of osilodrostat | Participants in the Expansion cohort who took 30mg of osilodrostat |
| Measure Participants | 4 | 13 | 6 | 1 | 1 |
| AUC0-6h,ss |
37.79
(42.7)
|
94.21
(37.0)
|
236.83
(29.9)
|
NA
(NA)
|
NA
(NA)
|
| AUC0-12h,ss |
69.96
(32.6)
|
140.65
(43.9)
|
339.62
(37.6)
|
NA
(NA)
|
NA
(NA)
|
| Title | PK Parameters: Cmax ss, Ctrough ss |
|---|---|
| Description | Trough PK concentrations and PK profiles at steady-state were collected. |
| Time Frame | pre-dose (0 hour), 1, 1.5, 2, 4 and 6 hours post AM dose for escalation dose or pre-dose (trough) for maintained dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PAS: all enrolled patients with at least 1 dose of study drug and at least 1 post-dose PK assessment after Protocol Amendment 4 or after re-entering the study. |
| Arm/Group Title | 2mg Bid | 5mg Bid | 10mg Bid | 20mg Bid | 30mg Bid |
|---|---|---|---|---|---|
| Arm/Group Description | Participants in the Expansion cohort who took 2mg of osilodrostat | Participants in the Expansion cohort who took 5mg of osilodrostat | Participants in the Expansion cohort who took 10mg of osilodrostat | Participants in the Expansion cohort who took 20mg of osilodrostat | Participants in the Expansion cohort who took 30mg of osilodrostat |
| Measure Participants | 6 | 14 | 8 | 2 | 1 |
| Cmax,ss |
8.76
(46.1)
|
23.09
(31.5)
|
59.17
(25.5)
|
NA
(NA)
|
NA
(NA)
|
| Ctrough, ss |
2.73
(49.1)
|
4.30
(112.9)
|
10.60
(104.8)
|
19.69
(53.6)
|
NA
(NA)
|
| Title | PK Parameters: Tmax ss, |
|---|---|
| Description | Trough PK concentrations and PK profiles at steady-state were collected. |
| Time Frame | pre-dose (0 hour), 1, 1.5, 2, 4 and 6 hours post AM dose for escalation dose or pre-dose (trough) for maintained dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PAS: all enrolled patients with at least 1 dose of study drug and at least 1 post-dose PK assessment after Protocol Amendment 4 or after re-entering the study. |
| Arm/Group Title | 2mg Bid | 5mg Bid | 10mg Bid | 20mg Bid | 30mg Bid |
|---|---|---|---|---|---|
| Arm/Group Description | Participants in the Expansion cohort who took 2mg of osilodrostat | Participants in the Expansion cohort who took 5mg of osilodrostat | Participants in the Expansion cohort who took 10mg of osilodrostat | Participants in the Expansion cohort who took 20mg of osilodrostat | Participants in the Expansion cohort who took 30mg of osilodrostat |
| Measure Participants | 4 | 13 | 6 | 1 | 1 |
| Median (Full Range) [hour (hr)] |
1.50
|
1.50
|
1.26
|
NA
|
NA
|
| Title | PK Parameters: T1/2 ss, |
|---|---|
| Description | Trough PK concentrations and PK profiles at steady-state were collected. |
| Time Frame | pre-dose (0 hour), 1, 1.5, 2, 4 and 6 hours post AM dose for escalation dose or pre-dose (trough) for maintained dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PAS: all enrolled patients with at least 1 dose of study drug and at least 1 post-dose PK assessment after Protocol Amendment 4 or after re-entering the study. |
| Arm/Group Title | 2mg Bid | 5mg Bid | 10mg Bid | 20mg Bid | 30mg Bid |
|---|---|---|---|---|---|
| Arm/Group Description | Participants in the Expansion cohort who took 2mg of osilodrostat | Participants in the Expansion cohort who took 5mg of osilodrostat | Participants in the Expansion cohort who took 10mg of osilodrostat | Participants in the Expansion cohort who took 20mg of osilodrostat | Participants in the Expansion cohort who took 30mg of osilodrostat |
| Measure Participants | 2 | 11 | 6 | 1 | 1 |
| Geometric Mean (Geometric Coefficient of Variation) [hour (hr)] |
6.39
(13.8)
|
3.54
(49.8)
|
4.32
(47.8)
|
NA
|
NA
|
| Title | Percentage of Participants Who Were Responders on 24-hour Urine Free Cortisol (UFC) at Week 22 |
|---|---|
| Description | A patient was considered to be a responder if his/her mean UFC level from the three 24-hour urine samples collected at Week 22 was ≤ ULN (as defined by the local laboratories) or represented a ≥50% decrease from baseline. Participants with controlled or partially controlled UFC were defined as: Controlled UFC: mean UFC level <= upper limit of normal (ULN). Partially controlled UFC: mean UFC level > ULN but with >= 50% reduction from baseline. |
| Time Frame | Week 22 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. This analysis was on the male patients only. |
| Arm/Group Title | Part II Core: Expansion Cohort | Part ll Core: Follow-up Cohort |
|---|---|---|
| Arm/Group Description | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Measure Participants | 15 | 4 |
| Responders |
80.0
666.7%
|
75.0
500%
|
| Controlled UFC responders |
80.0
666.7%
|
75.0
500%
|
| Partially controlled UFC responders |
0
0%
|
0
0%
|
| Title | Number of Participants With Escape |
|---|---|
| Description | Escape is defined as loss of UFC control (i.e. UFC > ULN) on at least 2 consecutive visits at the highest tolerated dose after previously attaining UFC normalization) |
| Time Frame | approx. 7 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. |
| Arm/Group Title | Part l: Core Cohort | Part II Core: Expansion Cohort |
|---|---|---|
| Arm/Group Description | Participants took an ascending dose of LCI699 (osilodrostat) from 2mg bid or 5 mg bid, up to 30 mg bid and participated in Part l of this study. 4 patients in this cohort moved to Part II of the study | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. |
| Measure Participants | 15 | 4 |
| Number [Participants] |
2
16.7%
|
0
0%
|
Adverse Events
| Time Frame | Adverse Event (AE) timeframe: Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment, up to maximum duration of 350.6 weeks. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse Event (AE): Any sign or symptom that occurs during the study treatment plus the 28 days post treatment | |||||
| Arm/Group Title | Part l: Core Cohort | Part ll Core: Expansion Cohort | Part ll Core: Follow-up Cohort | |||
| Arm/Group Description | Participants took an ascending dose of LCI699 (osilodrostat) from 2mg bid or 5 mg bid, up to 30 mg bid and participated in Part l of this study. 4 patients in this cohort moved to Part II of the study | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study | |||
All Cause Mortality |
||||||
| Part l: Core Cohort | Part ll Core: Expansion Cohort | Part ll Core: Follow-up Cohort | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | 0/15 (0%) | 0/4 (0%) | |||
Serious Adverse Events |
||||||
| Part l: Core Cohort | Part ll Core: Expansion Cohort | Part ll Core: Follow-up Cohort | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/12 (8.3%) | 5/15 (33.3%) | 1/4 (25%) | |||
| Cardiac disorders | ||||||
| Palpitations | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Supraventricular extrasystoles | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Tachycardia | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Ventricular extrasystoles | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Endocrine disorders | ||||||
| Adrenal insufficiency | 0/12 (0%) | 1/15 (6.7%) | 1/4 (25%) | |||
| Pituitary-dependent Cushing's syndrome | 0/12 (0%) | 2/15 (13.3%) | 0/4 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Food poisoning | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| General disorders | ||||||
| Non-cardiac chest pain | 1/12 (8.3%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Infections and infestations | ||||||
| Gastroenteritis | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Pyelonephritis | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Investigations | ||||||
| Electrocardiogram QT prolonged | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Haemoglobin decreased | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Neoplasm progression | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Pituitary tumour benign | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Nervous system disorders | ||||||
| Headache | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Vascular disorders | ||||||
| Takayasu's arteritis | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Part l: Core Cohort | Part ll Core: Expansion Cohort | Part ll Core: Follow-up Cohort | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 12/12 (100%) | 15/15 (100%) | 4/4 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 0/12 (0%) | 3/15 (20%) | 0/4 (0%) | |||
| Eosinophilia | 1/12 (8.3%) | 0/15 (0%) | 1/4 (25%) | |||
| Iron deficiency anaemia | 0/12 (0%) | 1/15 (6.7%) | 1/4 (25%) | |||
| Polycythaemia | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Cardiac disorders | ||||||
| Bradycardia | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Bundle branch block right | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Palpitations | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Sinus bradycardia | 1/12 (8.3%) | 1/15 (6.7%) | 1/4 (25%) | |||
| Tachycardia | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Ear and labyrinth disorders | ||||||
| Inner ear disorder | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Middle ear effusion | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Vertigo | 0/12 (0%) | 1/15 (6.7%) | 2/4 (50%) | |||
| Endocrine disorders | ||||||
| Adrenal insufficiency | 0/12 (0%) | 6/15 (40%) | 2/4 (50%) | |||
| Diabetes insipidus | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Glucocorticoid deficiency | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Hypothyroidism | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Pituitary-dependent Cushing's syndrome | 0/12 (0%) | 2/15 (13.3%) | 0/4 (0%) | |||
| Eye disorders | ||||||
| Blepharospasm | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Conjunctival haemorrhage | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Visual impairment | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 2/12 (16.7%) | 0/15 (0%) | 0/4 (0%) | |||
| Abdominal distension | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Abdominal pain | 2/12 (16.7%) | 2/15 (13.3%) | 3/4 (75%) | |||
| Abdominal pain upper | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Constipation | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Diarrhoea | 3/12 (25%) | 4/15 (26.7%) | 3/4 (75%) | |||
| Dry mouth | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Dyspepsia | 0/12 (0%) | 2/15 (13.3%) | 0/4 (0%) | |||
| Dysphagia | 1/12 (8.3%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Gastric disorder | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Gastrointestinal disorder | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Gastrointestinal pain | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Gastrooesophageal reflux disease | 0/12 (0%) | 1/15 (6.7%) | 1/4 (25%) | |||
| Haemorrhoidal haemorrhage | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Irritable bowel syndrome | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Nausea | 5/12 (41.7%) | 8/15 (53.3%) | 2/4 (50%) | |||
| Tongue disorder | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Toothache | 0/12 (0%) | 1/15 (6.7%) | 2/4 (50%) | |||
| Vomiting | 3/12 (25%) | 1/15 (6.7%) | 2/4 (50%) | |||
| General disorders | ||||||
| Asthenia | 0/12 (0%) | 5/15 (33.3%) | 2/4 (50%) | |||
| Chest discomfort | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Chills | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Fatigue | 7/12 (58.3%) | 3/15 (20%) | 3/4 (75%) | |||
| Feeling drunk | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Generalised oedema | 1/12 (8.3%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Influenza like illness | 1/12 (8.3%) | 0/15 (0%) | 1/4 (25%) | |||
| Malaise | 0/12 (0%) | 4/15 (26.7%) | 0/4 (0%) | |||
| Non-cardiac chest pain | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Oedema peripheral | 1/12 (8.3%) | 3/15 (20%) | 1/4 (25%) | |||
| Peripheral swelling | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Pyrexia | 0/12 (0%) | 2/15 (13.3%) | 0/4 (0%) | |||
| Hepatobiliary disorders | ||||||
| Cholelithiasis | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Hypertransaminasaemia | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Infections and infestations | ||||||
| Bronchitis | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Cystitis | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Escherichia urinary tract infection | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Fungal infection | 1/12 (8.3%) | 0/15 (0%) | 1/4 (25%) | |||
| Furuncle | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Gastroenteritis | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Gastroenteritis bacterial | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Groin abscess | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Helicobacter gastritis | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Herpes zoster | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Influenza | 0/12 (0%) | 2/15 (13.3%) | 1/4 (25%) | |||
| Laryngitis | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Lower respiratory tract infection | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Nasopharyngitis | 1/12 (8.3%) | 3/15 (20%) | 2/4 (50%) | |||
| Onychomycosis | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Pharyngitis streptococcal | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Sinusitis | 0/12 (0%) | 1/15 (6.7%) | 1/4 (25%) | |||
| Skin infection | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Tongue fungal infection | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Upper respiratory tract infection | 0/12 (0%) | 2/15 (13.3%) | 1/4 (25%) | |||
| Urinary tract infection | 1/12 (8.3%) | 3/15 (20%) | 3/4 (75%) | |||
| Viral rhinitis | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Vulvovaginal mycotic infection | 0/12 (0%) | 0/15 (0%) | 2/4 (50%) | |||
| Injury, poisoning and procedural complications | ||||||
| Accident | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Animal bite | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Arthropod bite | 2/12 (16.7%) | 3/15 (20%) | 0/4 (0%) | |||
| Contusion | 1/12 (8.3%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Foot fracture | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Heat illness | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Joint injury | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Ligament sprain | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Lumbar vertebral fracture | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Muscle injury | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Tooth fracture | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Investigations | ||||||
| Aldosterone urine increased | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Amylase increased | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Blood aldosterone decreased | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Blood alkaline phosphatase increased | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Blood corticotrophin increased | 0/12 (0%) | 5/15 (33.3%) | 3/4 (75%) | |||
| Blood creatine phosphokinase increased | 0/12 (0%) | 4/15 (26.7%) | 0/4 (0%) | |||
| Blood creatinine increased | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Blood gonadotrophin abnormal | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Blood lactate dehydrogenase increased | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Blood luteinising hormone decreased | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Blood phosphorus | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Blood potassium decreased | 0/12 (0%) | 1/15 (6.7%) | 1/4 (25%) | |||
| Blood pressure decreased | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Blood pressure increased | 0/12 (0%) | 2/15 (13.3%) | 0/4 (0%) | |||
| Blood prolactin increased | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Blood testosterone free increased | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Blood testosterone increased | 0/12 (0%) | 2/15 (13.3%) | 4/4 (100%) | |||
| Blood uric acid increased | 1/12 (8.3%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Cortisol decreased | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Cortisol free urine decreased | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Cortisol free urine increased | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Electrocardiogram T wave abnormal | 0/12 (0%) | 2/15 (13.3%) | 0/4 (0%) | |||
| Gamma-glutamyltransferase increased | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Gastric pH decreased | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Haemoglobin decreased | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Heart rate increased | 1/12 (8.3%) | 1/15 (6.7%) | 0/4 (0%) | |||
| High density lipoprotein decreased | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Hormone level abnormal | 0/12 (0%) | 4/15 (26.7%) | 3/4 (75%) | |||
| Lipase increased | 2/12 (16.7%) | 1/15 (6.7%) | 2/4 (50%) | |||
| Lymphocyte count decreased | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Neutrophil count increased | 0/12 (0%) | 0/15 (0%) | 2/4 (50%) | |||
| Oestradiol increased | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Platelet count decreased | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Protein total increased | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Renin decreased | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Urine analysis abnormal | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Urine leukocyte esterase | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Vitamin D decreased | 0/12 (0%) | 1/15 (6.7%) | 1/4 (25%) | |||
| Weight decreased | 0/12 (0%) | 2/15 (13.3%) | 0/4 (0%) | |||
| Weight increased | 1/12 (8.3%) | 2/15 (13.3%) | 1/4 (25%) | |||
| White blood cell count increased | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Folate deficiency | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Hypercalcaemia | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Hypercreatininaemia | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Hyperglycaemia | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Hyperkalaemia | 1/12 (8.3%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Hypernatraemia | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Hypertriglyceridaemia | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Hyperuricaemia | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Hypokalaemia | 3/12 (25%) | 1/15 (6.7%) | 2/4 (50%) | |||
| Hypomagnesaemia | 0/12 (0%) | 1/15 (6.7%) | 1/4 (25%) | |||
| Hypoproteinaemia | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Hyposideraemia | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Vitamin B12 deficiency | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Vitamin D deficiency | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 2/12 (16.7%) | 5/15 (33.3%) | 1/4 (25%) | |||
| Back pain | 1/12 (8.3%) | 2/15 (13.3%) | 0/4 (0%) | |||
| Bone pain | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Bursitis | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Joint effusion | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Joint swelling | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Muscle spasms | 3/12 (25%) | 1/15 (6.7%) | 1/4 (25%) | |||
| Muscular weakness | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Musculoskeletal chest pain | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Musculoskeletal pain | 0/12 (0%) | 2/15 (13.3%) | 1/4 (25%) | |||
| Musculoskeletal stiffness | 0/12 (0%) | 2/15 (13.3%) | 0/4 (0%) | |||
| Myalgia | 0/12 (0%) | 1/15 (6.7%) | 1/4 (25%) | |||
| Neck pain | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Osteopenia | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Pain in extremity | 1/12 (8.3%) | 2/15 (13.3%) | 0/4 (0%) | |||
| Tendonitis | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Neoplasm progression | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Pituitary tumour benign | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Nervous system disorders | ||||||
| Cold-stimulus headache | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Dizziness | 2/12 (16.7%) | 3/15 (20%) | 1/4 (25%) | |||
| Dizziness postural | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Headache | 3/12 (25%) | 6/15 (40%) | 2/4 (50%) | |||
| Hypersomnia | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Hypoaesthesia | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Hypogeusia | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Paraesthesia | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Presyncope | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Somnolence | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Syncope | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Psychiatric disorders | ||||||
| Abnormal sleep-related event | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Anxiety | 1/12 (8.3%) | 2/15 (13.3%) | 0/4 (0%) | |||
| Depression | 1/12 (8.3%) | 2/15 (13.3%) | 1/4 (25%) | |||
| Disorientation | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Insomnia | 0/12 (0%) | 1/15 (6.7%) | 1/4 (25%) | |||
| Libido decreased | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Sleep disorder | 0/12 (0%) | 1/15 (6.7%) | 1/4 (25%) | |||
| Renal and urinary disorders | ||||||
| Chromaturia | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Haematuria | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Nephrolithiasis | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Urinary incontinence | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Amenorrhoea | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Breast pain | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Dysmenorrhoea | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Erectile dysfunction | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Menorrhagia | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Menstruation delayed | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Oligomenorrhoea | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Vaginal haemorrhage | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asthma | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Cough | 1/12 (8.3%) | 2/15 (13.3%) | 0/4 (0%) | |||
| Dysphonia | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Dyspnoea | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Epistaxis | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Laryngeal oedema | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Nasal congestion | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Oropharyngeal pain | 1/12 (8.3%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Rhinitis allergic | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Sinus congestion | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Acanthosis nigricans | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Acne | 1/12 (8.3%) | 3/15 (20%) | 0/4 (0%) | |||
| Dermal cyst | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Dermatitis contact | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Dry skin | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Ecchymosis | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Hair growth abnormal | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Hirsutism | 0/12 (0%) | 2/15 (13.3%) | 0/4 (0%) | |||
| Hyperhidrosis | 1/12 (8.3%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Hypertrichosis | 0/12 (0%) | 1/15 (6.7%) | 2/4 (50%) | |||
| Melanoderma | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Night sweats | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Papule | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Pruritus | 2/12 (16.7%) | 1/15 (6.7%) | 1/4 (25%) | |||
| Rash | 0/12 (0%) | 3/15 (20%) | 0/4 (0%) | |||
| Skin discolouration | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Skin hyperpigmentation | 0/12 (0%) | 1/15 (6.7%) | 0/4 (0%) | |||
| Urticaria | 1/12 (8.3%) | 0/15 (0%) | 0/4 (0%) | |||
| Vascular disorders | ||||||
| Hot flush | 0/12 (0%) | 0/15 (0%) | 1/4 (25%) | |||
| Hypertension | 0/12 (0%) | 3/15 (20%) | 1/4 (25%) | |||
| Hypotension | 1/12 (8.3%) | 0/15 (0%) | 1/4 (25%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
| novartis.email@novartis.com |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01331239
Other Study ID Numbers:
- CLCI699C2201
- 2010-022403-22
First Posted:
Apr 8, 2011
Last Update Posted:
Jan 22, 2021
Last Verified:
Jan 1, 2021