Trial Outcomes & Findings for Induction and Maintenance of Castration After Subcutaneous Injections of Triptorelin Pamoate in Patients With Prostate Cancer (NCT NCT01715129)

Last Updated: 2019-12-09

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

126 participants

Primary outcome timeframe

At Day 29 and 183

Results posted on

2019-12-09

Participant Flow

A total of 139 subjects were screened and 13 subjects were screen failures.

Participant milestones

Participant milestones
Measure	Triptorelin Pamoate Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Overall Study STARTED	126
Overall Study COMPLETED	117
Overall Study NOT COMPLETED	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Triptorelin Pamoate Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Overall Study Adverse Event, fatal	1
Overall Study Lack of Efficacy	3
Overall Study Protocol Violation	1
Overall Study Consent Withdrawn	2
Overall Study Lost to Follow-up	1
Overall Study Other	1

Baseline Characteristics

Induction and Maintenance of Castration After Subcutaneous Injections of Triptorelin Pamoate in Patients With Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Triptorelin Pamoate n=126 Participants Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Age, Continuous	70.4 years STANDARD_DEVIATION 7.3 • n=5 Participants
Sex/Gender, Customized Male	126 participants n=5 Participants
Race/Ethnicity, Customized Caucasian / White	120 participants n=5 Participants
Race/Ethnicity, Customized Missing	6 participants n=5 Participants
Height	172.2 cm STANDARD_DEVIATION 6.7 • n=5 Participants
Weight	80.6 kg STANDARD_DEVIATION 12.8 • n=5 Participants
Body Mass Index (BMI)	27.16 kg/m² STANDARD_DEVIATION 3.96 • n=5 Participants
Prostate Specific Antigen (PSA)	133.53 ng/mL STANDARD_DEVIATION 385.60 • n=5 Participants

PRIMARY outcome

Timeframe: At Day 29 and 183

Population: N=Number of subjects attending the visit

Outcome measures

Outcome measures
Measure	Triptorelin Pamoate n=126 Participants Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Percentage of Subjects Demonstrating Castration at Day 29 and Maintaining Castration at Day 183 Day 29 (N=126)	97.6 Percentage of subjects Interval 93.2 to 99.5
Percentage of Subjects Demonstrating Castration at Day 29 and Maintaining Castration at Day 183 Day 183 (N=119)	96.6 Percentage of subjects Interval 91.6 to 99.1

SECONDARY outcome

Timeframe: At Day 92

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Triptorelin Pamoate n=120 Participants Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Percentage of Subjects Demonstrating Castration Before Administration of the Second Dose	99.2 Percentage of subjects Interval 95.4 to 100.0

SECONDARY outcome

Timeframe: Day 29 through Day 183

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

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

Outcome measures

Outcome measures
Measure	Triptorelin Pamoate n=126 Participants Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Probability of Testosterone <50 ng/dL	0.96 Proportion of subjects Interval 0.92 to 0.99

SECONDARY outcome

Timeframe: Day 95

Population: IC1 population.

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.

Outcome measures

Outcome measures
Measure	Triptorelin Pamoate n=119 Participants Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Percentage of Subjects Demonstrating Castration With Testosterone Level <50 ng/dL at Day 95	98.3 Percentage of subjects Interval 94.1 to 99.8

SECONDARY outcome

Timeframe: Up to Day 36

Population: ITT population

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)

Outcome measures

Outcome measures
Measure	Triptorelin Pamoate n=126 Participants Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Time to Achieve Castration (Tcast)	22 Day Interval 22.0 to 23.0

SECONDARY outcome

Timeframe: At Day 92 and 183

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

Outcome measures

Outcome measures
Measure	Triptorelin Pamoate n=122 Participants Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Plasma Triptorelin Levels (Cmin) Day 92	0.062 ng/mL Standard Deviation 0.031
Plasma Triptorelin Levels (Cmin) Day 183 (N=117)	0.049 ng/mL Standard Deviation 0.027

SECONDARY outcome

Timeframe: From Day 1 (Baseline) to Day 183 (End of study)

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

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.

Outcome measures

Outcome measures
Measure	Triptorelin Pamoate n=116 Participants Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Percentage Change in Prostate Specific Antigen (PSA) Levels From Baseline in All Subjects	-85.503 Percentage Change Standard Deviation 42.410

SECONDARY outcome

Timeframe: At Day 183

Population: Subjects completed Day 183 visit (End of Study)

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

Outcome measures

Outcome measures
Measure	Triptorelin Pamoate n=117 Participants Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Percentage of Subjects With Normal and Abnormal PSA Levels at Day 183 (End of Study Visit) End of Study (0-4 ng/mL)	84.6 Percentage of subjects
Percentage of Subjects With Normal and Abnormal PSA Levels at Day 183 (End of Study Visit) End of Study (>4 ng/mL)	15.4 Percentage of subjects

SECONDARY outcome

Timeframe: Day 92 and 183

Population: ITT population

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).

Outcome measures

Outcome measures
Measure	Triptorelin Pamoate n=126 Participants Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Clinically Apparent Tumor Progression Day 92: Non Progressive Disease	122 participants
Clinically Apparent Tumor Progression Day 92: Progressive Disease	0 participants
Clinically Apparent Tumor Progression Day 183: Non Progressive Disease	114 participants
Clinically Apparent Tumor Progression Day 183: Progressive Disease	3 participants

SECONDARY outcome

Timeframe: Up to Day 183

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

Outcome measures

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

SECONDARY outcome

Timeframe: At 1, 2, 3, 4, 5, 6, 7, 8 and 24 hours after first dose on Day 1

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

Outcome measures

Outcome measures
Measure	Triptorelin Pamoate n=18 Participants Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Time to Cmax (Tmax) of Triptorelin	4.5 Hours Interval 1.01 to 24.0

SECONDARY outcome

Timeframe: At 1, 2, 3, 4, 5, 6, 7, 8 and 24 hours after first dose on Day 1

Population: PK profile was assessed in a subset of 18 subjects.

Outcome measures

Outcome measures
Measure	Triptorelin Pamoate n=18 Participants Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Peak Plasma Concentration Value (Cmax) of Triptorelin	18.58 ng/mL Standard Deviation 7.35

SECONDARY outcome

Timeframe: At 1, 2, 3, 4, 5, 6, 7, 8 and 24 hours after first dose on Day 1

Population: PK profile was assessed in a subset of 18 subjects.

Outcome measures

Outcome measures
Measure	Triptorelin Pamoate n=18 Participants Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Area Under the Concentration Versus Time Curve Between 0 and 24 Hours (AUC0-24) of Triptorelin	304.6 h*ng/mL Standard Deviation 103.7

SECONDARY outcome

Timeframe: At Day 92 and 183

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

Outcome measures

Outcome measures
Measure	Triptorelin Pamoate n=18 Participants Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Cmin of Triptorelin in Subset of 18 Subjects Day 183 (N=18)	0.062 ng/mL Standard Deviation 0.023
Cmin of Triptorelin in Subset of 18 Subjects Day 92 (N=14)	0.078 ng/mL Standard Deviation 0.038

Adverse Events

Triptorelin Pamoate 11.25 mg

Serious events: 6 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Triptorelin Pamoate 11.25 mg n=126 participants at risk Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Injury, poisoning and procedural complications Fibula Fracture	0.79% 1/126 • Number of events 1 • Up to Day 183
Cardiac disorders Cardiac Failure	0.79% 1/126 • Number of events 1 • Up to Day 183
Cardiac disorders Myocardial infarction	0.79% 1/126 • Number of events 1 • Up to Day 183
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.79% 1/126 • Number of events 1 • Up to Day 183
Blood and lymphatic system disorders Anaemia	0.79% 1/126 • Number of events 1 • Up to Day 183
Infections and infestations Pneumonia	1.6% 2/126 • Number of events 2 • Up to Day 183

Other adverse events

Other adverse events
Measure	Triptorelin Pamoate 11.25 mg n=126 participants at risk Triptorelin Pamoate corresponding to 11.25 mg of triptorelin administered subcutaneously on Day 1 and 92
Vascular disorders Hot Flush	10.3% 13/126 • Number of events 13 • Up to Day 183
Vascular disorders Hypertension	4.8% 6/126 • Number of events 8 • Up to Day 183
Vascular disorders Flushing	0.79% 1/126 • Number of events 1 • Up to Day 183
Vascular disorders Haematoma	0.79% 1/126 • Number of events 1 • Up to Day 183
General disorders Oedema Peripheral	1.6% 2/126 • Number of events 2 • Up to Day 183
General disorders Asthenia	0.79% 1/126 • Number of events 1 • Up to Day 183
General disorders Chills	0.79% 1/126 • Number of events 1 • Up to Day 183
General disorders Fatigue	0.79% 1/126 • Number of events 1 • Up to Day 183
General disorders Hyperthermia	0.79% 1/126 • Number of events 1 • Up to Day 183
General disorders Injection Site Haematoma	0.79% 1/126 • Number of events 1 • Up to Day 183
General disorders Injection Site Pain	0.79% 1/126 • Number of events 1 • Up to Day 183
General disorders Injection Site Swelling	0.79% 1/126 • Number of events 1 • Up to Day 183
Psychiatric disorders Anger	0.79% 1/126 • Number of events 1 • Up to Day 183
Psychiatric disorders Nervousness	0.79% 1/126 • Number of events 1 • Up to Day 183
Reproductive system and breast disorders Erectile Dysfunction	2.4% 3/126 • Number of events 3 • Up to Day 183
Reproductive system and breast disorders Breast Pain	1.6% 2/126 • Number of events 2 • Up to Day 183
Reproductive system and breast disorders Breast Swelling	0.79% 1/126 • Number of events 1 • Up to Day 183
Reproductive system and breast disorders Breast Tenderness	0.79% 1/126 • Number of events 1 • Up to Day 183
Injury, poisoning and procedural complications Fall	1.6% 2/126 • Number of events 2 • Up to Day 183
Injury, poisoning and procedural complications Fibula Fracture	0.79% 1/126 • Number of events 1 • Up to Day 183
Injury, poisoning and procedural complications Wound	0.79% 1/126 • Number of events 1 • Up to Day 183
Injury, poisoning and procedural complications Wrist Fracture	0.79% 1/126 • Number of events 1 • Up to Day 183
Investigations Weight Increased	9.5% 12/126 • Number of events 12 • Up to Day 183
Investigations Weight Decreased	5.6% 7/126 • Number of events 7 • Up to Day 183
Investigations Blood Pressure Increased	0.79% 1/126 • Number of events 1 • Up to Day 183
Cardiac disorders Cardiac Failure	0.79% 1/126 • Number of events 1 • Up to Day 183
Cardiac disorders Myocardial Infarction	0.79% 1/126 • Number of events 1 • Up to Day 183
Blood and lymphatic system disorders Anaemia	0.79% 1/126 • Number of events 2 • Up to Day 183
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.79% 1/126 • Number of events 1 • Up to Day 183
Respiratory, thoracic and mediastinal disorders Cough	0.79% 1/126 • Number of events 1 • Up to Day 183
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.79% 1/126 • Number of events 1 • Up to Day 183
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.79% 1/126 • Number of events 1 • Up to Day 183
Nervous system disorders Headache	3.2% 4/126 • Number of events 12 • Up to Day 183
Nervous system disorders Loss Of Consciousness	0.79% 1/126 • Number of events 1 • Up to Day 183
Eye disorders Conjunctivitis	1.6% 2/126 • Number of events 2 • Up to Day 183
Renal and urinary disorders Dysuria	0.79% 1/126 • Number of events 1 • Up to Day 183
Renal and urinary disorders Haematuria	0.79% 1/126 • Number of events 1 • Up to Day 183
Renal and urinary disorders Nocturia	0.79% 1/126 • Number of events 1 • Up to Day 183
Renal and urinary disorders Pollakiuria	0.79% 1/126 • Number of events 1 • Up to Day 183
Renal and urinary disorders Urinary Retention	0.79% 1/126 • Number of events 1 • Up to Day 183
Skin and subcutaneous tissue disorders Hyperhidrosis	2.4% 3/126 • Number of events 3 • Up to Day 183
Skin and subcutaneous tissue disorders Night Sweats	1.6% 2/126 • Number of events 2 • Up to Day 183
Skin and subcutaneous tissue disorders Hypotrichosis	0.79% 1/126 • Number of events 1 • Up to Day 183
Skin and subcutaneous tissue disorders Pruritus	0.79% 1/126 • Number of events 1 • Up to Day 183
Musculoskeletal and connective tissue disorders Arthralgia	0.79% 1/126 • Number of events 1 • Up to Day 183
Musculoskeletal and connective tissue disorders Back Pain	0.79% 1/126 • Number of events 1 • Up to Day 183
Musculoskeletal and connective tissue disorders Haemarthrosis	0.79% 1/126 • Number of events 1 • Up to Day 183
Musculoskeletal and connective tissue disorders Pain In Extremity	0.79% 1/126 • Number of events 1 • Up to Day 183
Metabolism and nutrition disorders Hypokalaemia	0.79% 1/126 • Number of events 2 • Up to Day 183
Metabolism and nutrition disorders Hyperglycaemia	0.79% 1/126 • Number of events 1 • Up to Day 183
Metabolism and nutrition disorders Hyperkalaemia	0.79% 1/126 • Number of events 1 • Up to Day 183
Metabolism and nutrition disorders Hypomagnesaemia	0.79% 1/126 • Number of events 1 • Up to Day 183
Infections and infestations Pneumonia	1.6% 2/126 • Number of events 2 • Up to Day 183
Infections and infestations Bronchitis	0.79% 1/126 • Number of events 1 • Up to Day 183
Infections and infestations Ear Infection	0.79% 1/126 • Number of events 1 • Up to Day 183
Infections and infestations Influenza	0.79% 1/126 • Number of events 1 • Up to Day 183
Infections and infestations Nasopharyngitis	0.79% 1/126 • Number of events 1 • Up to Day 183
Infections and infestations Tooth Abscess	0.79% 1/126 • Number of events 1 • Up to Day 183

Additional Information

Medical Director, Oncology

Ipsen

Phone: [email protected]

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place