DKP 3M SC: Induction and Maintenance of Castration After Subcutaneous Injections of Triptorelin Pamoate in Patients With Prostate Cancer

• Sponsor: Ipsen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01715129
• Collaborator: (none)
• Enrollment: 126
• Locations: 12
• Arm: 1
• Duration (Months): 9
• Patients Per Site: 10.5
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

Assess the efficacy and safety of Triptorelin pamoate 3M formulation (11.25mg) when administered by subcutaneous route.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Triptorelin Pamoate 11.25mg	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 126 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Single Arm Study to Evaluate the Efficacy, Safety and Local Tolerability of a Subcutaneous 3-month Formulation of Triptorelin Pamoate (11.25 mg) in Patients With Locally Advanced or Metastatic Prostate Cancer
• Study Start Date: Jan 1, 2013
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 11.25mg 11.25mg, SC on Day 1 and Day 92	Drug: Triptorelin Pamoate 11.25mg

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects Demonstrating Castration at Day 29 and Maintaining Castration at Day 183 [At Day 29 and 183]

   Percentage of subjects castrated (i.e. with serum testosterone <50 ng/dL or 1.735 nmol/L, using the LC-MS/MS method and missing data imputed by immunoassay method (at time points when LC-MS/MS data was planned to be available only) and the proportion with castration maintained at Day 183 (after receiving 2 S.C. administrations of triptorelin pamoate, three months apart); they were calculated along with their respective 95% confidence intervals (CI) using exact methods on the ITT population at Day 29 and on the initially castrated (IC) population at Day 183

Secondary Outcome Measures

1. Percentage of Subjects Demonstrating Castration Before Administration of the Second Dose [At Day 92]

   Percentage of subjects demonstrating castration at Day 92 (before administration of the second dose) were also assessed using the LC-MS/MS method and missing data imputed by immunoassay method (at time points when LC-MS/MS data was planned to be available only) and summarised using descriptive statistics on the ITT and IC populations.

2. Probability of Testosterone <50 ng/dL [Day 29 through Day 183]

   Probability of testosterone <50 ng/dL from Day 29 to Day 183 was assessed as a secondary endpoint using the time to event from first administration date to first observed (and subsequently confirmed if assessment not performed at end of study or early withdrawal visits) serum testosterone level ≥50 ng/dL or ≥1.735 nmol/L at or after Day 29, assessed using the LC-MS/MS Method and Missing Data imputed by immunoassay method Kaplan-Meier Analysis. LC-MS/MS: Liquid Chromatography-Tandem Mass Spectrometry

3. Percentage of Subjects Demonstrating Castration With Testosterone Level <50 ng/dL at Day 95 [Day 95]

   Percentage of subjects demonstrating castration at Day 95 (3-4 days after administration of the second dose to assess the suppression of acute-on-chronic effect following the second administration) were also assessed using the LC-MS/MS method and missing data imputed by immunoassay method (at time points when LC-MS/MS data was planned to be available only) and summarised using descriptive statistics on the ITT and IC populations.

4. Time to Achieve Castration (Tcast) [Up to Day 36]

   Time to castration (Tcast) from first administration date until first observed serum testosterone level <50 ng/dL or <1.735 nmol/L evaluated using the immunoassay method only (i.e. defined as the number of days between the injection time at Day 1 and castration achievement)

5. Plasma Triptorelin Levels (Cmin) [At Day 92 and 183]

   Minimal triptorelin plasma concentration at the end of each dosage interval just before the next dose injection (Cmin) for Days 92 and 183 were assessed.

6. Percentage Change in Prostate Specific Antigen (PSA) Levels From Baseline in All Subjects [From Day 1 (Baseline) to Day 183 (End of study)]

   Serum PSA level was presented throughout the study using descriptive statistics displaying raw values, change from Baseline and percentage change from Baseline at each visit in all subjects from the ITT population only. Additionally, the PSA level was described in subjects with elevated PSA levels (i.e. >4 ng/mL) at study entry, and the proportion of subjects with normal PSA levels (i.e. [0-4] ng/mL) at Day 183 compared to Baseline was presented.

7. Percentage of Subjects With Normal and Abnormal PSA Levels at Day 183 (End of Study Visit) [At Day 183]

   0-4 ng/mL (normal PSA value) >4 ng/mL (abnormal PSA levels)

8. Clinically Apparent Tumor Progression [Day 92 and 183]

   Tumour progression was recorded according to the Investigator's clinical judgement, considering the PSA levels and any other indications of disease; the clinical confirmation might be supplemented by radiological or other investigations or scans if required. The lack of clinically apparent tumour progression was assessed at Day 92 (prior to administration of the second dose) and Day 183 (end of study visit).

9. Percentage of Subjects With Adverse Events [Up to Day 183]

10. Time to Cmax (Tmax) of Triptorelin [At 1, 2, 3, 4, 5, 6, 7, 8 and 24 hours after first dose on Day 1]

11. Peak Plasma Concentration Value (Cmax) of Triptorelin [At 1, 2, 3, 4, 5, 6, 7, 8 and 24 hours after first dose on Day 1]

12. Area Under the Concentration Versus Time Curve Between 0 and 24 Hours (AUC0-24) of Triptorelin [At 1, 2, 3, 4, 5, 6, 7, 8 and 24 hours after first dose on Day 1]

13. Cmin of Triptorelin in Subset of 18 Subjects [At Day 92 and 183]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically proven locally advanced or metastatic prostate cancer who are suitable for androgen deprivation therapy

• Male aged ≥18 years old

• Screening testosterone level of >125 ng/dL

• Life expectancy of greater than 12 months in the judgement of the Investigator

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

• Willing to give signed informed consent freely

• Able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

• Prior hormonal therapy for prostate cancer

• Prior surgery or radiotherapy of prostate cancer with curative intent unless disease is verified by a rising prostate specific antigen (PSA) concentration on follow up (elevated PSA values on last two tests conducted at least a month apart) and the patient is eligible for androgen deprivation therapy

• Presence or history of any other malignancy except for non melanoma skin cancer adequately treated at least 2 years before study entry

• Painful local bone lesions or spinal lesions which may lead to compression

• History of myocardial infarction, percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass graft, Class III/IV congestive heart failure, cerebrovascular accident, transient ischaemic attack, or limb claudication at rest, within six months prior to start of study treatment and ongoing symptomatic dysrhythmias, unstable angina, uncontrolled hypertension, and untreated atrial or uncontrolled ventricular arrhythmias

• Any condition in opinion of the Investigator, including other active or latent infections, medical or psychiatric conditions, or the presence of laboratory abnormalities, which could confound the ability to interpret data from the study, compromises the objective of the study or places the patient at unacceptable risk if he participates in the study

• Abnormal haematological, hepatic or renal functions:

• Haemoglobin <9 g/dL, absolute neutrophil count ≤1.5 x 10^{9/L or platelets ≤100 x 10}9/L

• Serum creatinine ≥1.5 times the upper limit of normal (ULN)

• Aspartate aminotransferase or alanine aminotransferase >2.5 times the ULN

• Known hypersensitivity to the study treatment, to any of its excipients

• Known active use of recreational drug or alcohol dependence in the opinion of the Investigator

• Any current use or use within six months prior to start of treatment, of medications which are known to affect the metabolism and/or secretion of androgenic hormones: e.g. ketoconazole, aminoglutethimide, oestrogens, and progesterone

• Use of systemic corticosteroids (inhaled corticosteroids and topical application of corticosteroids are permitted)

• Aged ≥90 years for the main study and ≥80 years for those included in the pharmacokinetic (PK) patient population

• Participation in any other study or receipt of any investigational compound in the 30 days (or five times the elimination half life if this is longer) prior to study entry

• Any skin or other condition that may preclude s.c. injection administration

• Known brain or epidural metastases.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Pleven		Bulgaria
2		Plovdiv		Bulgaria
3		Shumen		Bulgaria
4		Varna		Bulgaria
5		Suresnes		France
6		Daugavpils		Latvia
7		Riga		Latvia
8		Kutno		Poland
9		Warsaw		Poland
10		Wroclaw		Poland
11		Bucharest		Romania
12		Craiova		Romania

Sponsors and Collaborators

• Ipsen

Investigators

• Study Director: Medical Director, Uro-Oncology, Ipsen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT01715129
• Other Study ID Numbers: 8-55-52014-200; 2012-001279-35
• First Posted: Oct 26, 2012
• Last Update Posted: Dec 9, 2019
• Last Verified: Nov 1, 2019

• Additional relevant MeSH terms: Prostatic Neoplasms; Triptorelin Pamoate

Study Results

Participant Flow

Pre-assignment Detail	A total of 139 subjects were screened and 13 subjects were screen failures.

Arm/Group Title	Triptorelin Pamoate
Arm/Group Description	Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Period Title: Overall Study
STARTED	126
COMPLETED	117
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	Triptorelin Pamoate
Arm/Group Description	Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Overall Participants	126
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.4 (7.3)
Sex/Gender, Customized (participants) [Number]
Male	126 100%
Race/Ethnicity, Customized (participants) [Number]
Caucasian / White	120 95.2%
Missing	6 4.8%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	172.2 (6.7)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	80.6 (12.8)
Body Mass Index (BMI) (kg/m²) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m²]	27.16 (3.96)
Prostate Specific Antigen (PSA) (ng/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/mL]	133.53 (385.60)

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects Demonstrating Castration at Day 29 and Maintaining Castration at Day 183
Description	Percentage of subjects castrated (i.e. with serum testosterone <50 ng/dL or 1.735 nmol/L, using the LC-MS/MS method and missing data imputed by immunoassay method (at time points when LC-MS/MS data was planned to be available only) and the proportion with castration maintained at Day 183 (after receiving 2 S.C. administrations of triptorelin pamoate, three months apart); they were calculated along with their respective 95% confidence intervals (CI) using exact methods on the ITT population at Day 29 and on the initially castrated (IC) population at Day 183
Time Frame	At Day 29 and 183

Outcome Measure Data

Analysis Population Description

N=Number of subjects attending the visit

Arm/Group Title	Triptorelin Pamoate
Arm/Group Description	Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Measure Participants	126
Day 29 (N=126)	97.6
Day 183 (N=119)	96.6

2. Secondary Outcome

Title	Percentage of Subjects Demonstrating Castration Before Administration of the Second Dose
Description	Percentage of subjects demonstrating castration at Day 92 (before administration of the second dose) were also assessed using the LC-MS/MS method and missing data imputed by immunoassay method (at time points when LC-MS/MS data was planned to be available only) and summarised using descriptive statistics on the ITT and IC populations.
Time Frame	At Day 92

Outcome Measure Data

Analysis Population Description

Initially Castrated (IC1) population: All treated subjects with testosterone levels <50 ng/dL at Day 29 or at Day 36, assessed with the LC-MS/MS method and missing data imputed by immunoassay method.

Arm/Group Title	Triptorelin Pamoate
Arm/Group Description	Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Measure Participants	120
Number (95% Confidence Interval) [Percentage of subjects]	99.2

3. Secondary Outcome

Title	Probability of Testosterone <50 ng/dL
Description	Probability of testosterone <50 ng/dL from Day 29 to Day 183 was assessed as a secondary endpoint using the time to event from first administration date to first observed (and subsequently confirmed if assessment not performed at end of study or early withdrawal visits) serum testosterone level ≥50 ng/dL or ≥1.735 nmol/L at or after Day 29, assessed using the LC-MS/MS Method and Missing Data imputed by immunoassay method Kaplan-Meier Analysis. LC-MS/MS: Liquid Chromatography-Tandem Mass Spectrometry
Time Frame	Day 29 through Day 183

Outcome Measure Data

Analysis Population Description

Intention-to-treat (ITT) population: All treated subjects

Arm/Group Title	Triptorelin Pamoate
Arm/Group Description	Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Measure Participants	126
Number (95% Confidence Interval) [Proportion of subjects]	0.96

4. Secondary Outcome

Title	Percentage of Subjects Demonstrating Castration With Testosterone Level <50 ng/dL at Day 95
Description	Percentage of subjects demonstrating castration at Day 95 (3-4 days after administration of the second dose to assess the suppression of acute-on-chronic effect following the second administration) were also assessed using the LC-MS/MS method and missing data imputed by immunoassay method (at time points when LC-MS/MS data was planned to be available only) and summarised using descriptive statistics on the ITT and IC populations.
Time Frame	Day 95

Outcome Measure Data

Analysis Population Description

IC1 population.

Arm/Group Title	Triptorelin Pamoate
Arm/Group Description	Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Measure Participants	119
Number (95% Confidence Interval) [Percentage of subjects]	98.3

5. Secondary Outcome

Title	Time to Achieve Castration (Tcast)
Description	Time to castration (Tcast) from first administration date until first observed serum testosterone level <50 ng/dL or <1.735 nmol/L evaluated using the immunoassay method only (i.e. defined as the number of days between the injection time at Day 1 and castration achievement)
Time Frame	Up to Day 36

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Triptorelin Pamoate
Arm/Group Description	Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Measure Participants	126
Median (95% Confidence Interval) [Day]	22

6. Secondary Outcome

Title	Plasma Triptorelin Levels (Cmin)
Description	Minimal triptorelin plasma concentration at the end of each dosage interval just before the next dose injection (Cmin) for Days 92 and 183 were assessed.
Time Frame	At Day 92 and 183

Outcome Measure Data

Analysis Population Description

ITT population. No samples were collected from 4 subjects at Day 92 and 9 subjects at Day 183

Arm/Group Title	Triptorelin Pamoate
Arm/Group Description	Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Measure Participants	122
Day 92	0.062 (0.031)
Day 183 (N=117)	0.049 (0.027)

7. Secondary Outcome

Title	Percentage Change in Prostate Specific Antigen (PSA) Levels From Baseline in All Subjects
Description	Serum PSA level was presented throughout the study using descriptive statistics displaying raw values, change from Baseline and percentage change from Baseline at each visit in all subjects from the ITT population only. Additionally, the PSA level was described in subjects with elevated PSA levels (i.e. >4 ng/mL) at study entry, and the proportion of subjects with normal PSA levels (i.e. [0-4] ng/mL) at Day 183 compared to Baseline was presented.
Time Frame	From Day 1 (Baseline) to Day 183 (End of study)

Outcome Measure Data

Analysis Population Description

ITT population at End of Study (Day 183). One subject had no data.

Arm/Group Title	Triptorelin Pamoate
Arm/Group Description	Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Measure Participants	116
Mean (Standard Deviation) [Percentage Change]	-85.503 (42.410)

8. Secondary Outcome

Title	Percentage of Subjects With Normal and Abnormal PSA Levels at Day 183 (End of Study Visit)
Description	0-4 ng/mL (normal PSA value) >4 ng/mL (abnormal PSA levels)
Time Frame	At Day 183

Outcome Measure Data

Analysis Population Description

Subjects completed Day 183 visit (End of Study)

Arm/Group Title	Triptorelin Pamoate
Arm/Group Description	Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Measure Participants	117
End of Study (0-4 ng/mL)	84.6
End of Study (>4 ng/mL)	15.4

9. Secondary Outcome

Title	Clinically Apparent Tumor Progression
Description	Tumour progression was recorded according to the Investigator's clinical judgement, considering the PSA levels and any other indications of disease; the clinical confirmation might be supplemented by radiological or other investigations or scans if required. The lack of clinically apparent tumour progression was assessed at Day 92 (prior to administration of the second dose) and Day 183 (end of study visit).
Time Frame	Day 92 and 183

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Triptorelin Pamoate
Arm/Group Description	Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Measure Participants	126
Day 92: Non Progressive Disease	122 96.8%
Day 92: Progressive Disease	0 0%
Day 183: Non Progressive Disease	114 90.5%
Day 183: Progressive Disease	3 2.4%

10. Secondary Outcome

Title	Percentage of Subjects With Adverse Events
Time Frame	Up to Day 183

Outcome Measure Data

Analysis Population Description

All subjects who received at least one dose of study treatment were included in safety population.

Arm/Group Title	Triptorelin Pamoate
Arm/Group Description	Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Measure Participants	126
Any Adverse Events	35.7
Any Serious Adverse Events (SAEs)	4.8
Any Treatment Emergent Adverse Events (TEAEs)	35.7
TEAEs Leading to Withdrawal	0.8
TEAEs Leading to Death	0.8
Maximum Grade NCI-CTC of TEAEs: Grade 5	0.8
Maximum Grade NCI-CTC of TEAEs: Grade 4	0
Maximum Grade NCI-CTC of TEAEs: Grade 3	4.0
Maximum Grade NCI-CTC of TEAEs: Grade 2	13.5
Maximum Grade NCI-CTC of TEAEs: Grade 1	27.8
Most serious causality of TEAEs: Related	21.4
Most serious causality of TEAEs: Not related	26.2

11. Secondary Outcome

Title	Time to Cmax (Tmax) of Triptorelin
Time Frame	At 1, 2, 3, 4, 5, 6, 7, 8 and 24 hours after first dose on Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) profile was assessed in a subset of 18 subjects.

Arm/Group Title	Triptorelin Pamoate
Arm/Group Description	Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Measure Participants	18
Median (Full Range) [Hours]	4.5

12. Secondary Outcome

Title	Peak Plasma Concentration Value (Cmax) of Triptorelin
Time Frame	At 1, 2, 3, 4, 5, 6, 7, 8 and 24 hours after first dose on Day 1

Outcome Measure Data

Analysis Population Description

PK profile was assessed in a subset of 18 subjects.

Arm/Group Title	Triptorelin Pamoate
Arm/Group Description	Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Measure Participants	18
Mean (Standard Deviation) [ng/mL]	18.58 (7.35)

13. Secondary Outcome

Title	Area Under the Concentration Versus Time Curve Between 0 and 24 Hours (AUC0-24) of Triptorelin
Time Frame	At 1, 2, 3, 4, 5, 6, 7, 8 and 24 hours after first dose on Day 1

Outcome Measure Data

Analysis Population Description

PK profile was assessed in a subset of 18 subjects.

Arm/Group Title	Triptorelin Pamoate
Arm/Group Description	Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Measure Participants	18
Mean (Standard Deviation) [h*ng/mL]	304.6 (103.7)

14. Secondary Outcome

Title	Cmin of Triptorelin in Subset of 18 Subjects
Time Frame	At Day 92 and 183

Outcome Measure Data

Analysis Population Description

Day 92: Four subjects (presenting particularly high levels of triptorelin) were excluded from 18-subject subset.

Arm/Group Title	Triptorelin Pamoate
Arm/Group Description	Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Measure Participants	18
Day 92 (N=14)	0.078 (0.038)
Day 183 (N=18)	0.062 (0.023)

Adverse Events

Time Frame	Up to Day 183
Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
All Cause Mortality
	Triptorelin Pamoate 11.25 mg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Triptorelin Pamoate 11.25 mg
	Affected / at Risk (%)	# Events
Total	6/126 (4.8%)
Blood and lymphatic system disorders
Anaemia	1/126 (0.8%)	1
Cardiac disorders
Cardiac Failure	1/126 (0.8%)	1
Myocardial infarction	1/126 (0.8%)	1
Infections and infestations
Pneumonia	2/126 (1.6%)	2
Injury, poisoning and procedural complications
Fibula Fracture	1/126 (0.8%)	1
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease	1/126 (0.8%)	1
Other (Not Including Serious) Adverse Events
	Triptorelin Pamoate 11.25 mg
	Affected / at Risk (%)	# Events
Total	45/126 (35.7%)
Blood and lymphatic system disorders
Anaemia	1/126 (0.8%)	2
Cardiac disorders
Cardiac Failure	1/126 (0.8%)	1
Myocardial Infarction	1/126 (0.8%)	1
Eye disorders
Conjunctivitis	2/126 (1.6%)	2
General disorders
Oedema Peripheral	2/126 (1.6%)	2
Asthenia	1/126 (0.8%)	1
Chills	1/126 (0.8%)	1
Fatigue	1/126 (0.8%)	1
Hyperthermia	1/126 (0.8%)	1
Injection Site Haematoma	1/126 (0.8%)	1
Injection Site Pain	1/126 (0.8%)	1
Injection Site Swelling	1/126 (0.8%)	1
Infections and infestations
Pneumonia	2/126 (1.6%)	2
Bronchitis	1/126 (0.8%)	1
Ear Infection	1/126 (0.8%)	1
Influenza	1/126 (0.8%)	1
Nasopharyngitis	1/126 (0.8%)	1
Tooth Abscess	1/126 (0.8%)	1
Injury, poisoning and procedural complications
Fall	2/126 (1.6%)	2
Fibula Fracture	1/126 (0.8%)	1
Wound	1/126 (0.8%)	1
Wrist Fracture	1/126 (0.8%)	1
Investigations
Weight Increased	12/126 (9.5%)	12
Weight Decreased	7/126 (5.6%)	7
Blood Pressure Increased	1/126 (0.8%)	1
Metabolism and nutrition disorders
Hypokalaemia	1/126 (0.8%)	2
Hyperglycaemia	1/126 (0.8%)	1
Hyperkalaemia	1/126 (0.8%)	1
Hypomagnesaemia	1/126 (0.8%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/126 (0.8%)	1
Back Pain	1/126 (0.8%)	1
Haemarthrosis	1/126 (0.8%)	1
Pain In Extremity	1/126 (0.8%)	1
Nervous system disorders
Headache	4/126 (3.2%)	12
Loss Of Consciousness	1/126 (0.8%)	1
Psychiatric disorders
Anger	1/126 (0.8%)	1
Nervousness	1/126 (0.8%)	1
Renal and urinary disorders
Dysuria	1/126 (0.8%)	1
Haematuria	1/126 (0.8%)	1
Nocturia	1/126 (0.8%)	1
Pollakiuria	1/126 (0.8%)	1
Urinary Retention	1/126 (0.8%)	1
Reproductive system and breast disorders
Erectile Dysfunction	3/126 (2.4%)	3
Breast Pain	2/126 (1.6%)	2
Breast Swelling	1/126 (0.8%)	1
Breast Tenderness	1/126 (0.8%)	1
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease	1/126 (0.8%)	1
Cough	1/126 (0.8%)	1
Dyspnoea	1/126 (0.8%)	1
Haemoptysis	1/126 (0.8%)	1
Skin and subcutaneous tissue disorders
Hyperhidrosis	3/126 (2.4%)	3
Night Sweats	2/126 (1.6%)	2
Hypotrichosis	1/126 (0.8%)	1
Pruritus	1/126 (0.8%)	1
Vascular disorders
Hot Flush	13/126 (10.3%)	13
Hypertension	6/126 (4.8%)	8
Flushing	1/126 (0.8%)	1
Haematoma	1/126 (0.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.