Trial Outcomes & Findings for Equivalence of Intramuscular (IM) Versus Subcutaneous (SC) Applications of Long Acting Pamorelin 11.25 mg (NCT NCT01257425)

Last Updated: 2019-02-08

Results Overview

Area under the curve (AUC) calculated from serum testosterone concentration taken at intervals between the first administration (Day 1) of the study drug and Day 85 after dosing. From the curve describing serum testosterone concentration levels (ng/mL) over time, the AUC was calculated using numerical integration methods. This value was log-transformed to more closely meet the assumption of the statistical method.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

109 participants

Primary outcome timeframe

1, 3, 5, 8, 15, 22, 29, 57, 85 days post-dose

Results posted on

2019-02-08

Participant Flow

Patients diagnosed with advanced prostate cancer (locally advanced or metastatic, histologically proven) recruited at 23 investigational sites in Germany.

109 patients screened and 6 of these did not fulfil randomisation criteria therefore 103 patients were randomised to either group of treatment with triptorelin pamoate 3-month formulation applied intramuscularly or subcutaneously.

Participant milestones

Participant milestones
Measure	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85.	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM. Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85.
Overall Study STARTED	52	51
Overall Study COMPLETED	46	45
Overall Study NOT COMPLETED	6	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85.	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM. Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85.
Overall Study Lack of Efficacy	3	3
Overall Study Adverse Event	1	1
Overall Study Protocol Violation	1	1
Overall Study Withdrawal by Subject	0	1
Overall Study Death	1	0

Baseline Characteristics

Equivalence of Intramuscular (IM) Versus Subcutaneous (SC) Applications of Long Acting Pamorelin 11.25 mg

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. n=52 Participants Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85.	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM. n=51 Participants Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85.	Total n=103 Participants Total of all reporting groups
Age, Continuous	73.4 years STANDARD_DEVIATION 6.7 • n=93 Participants	73.3 years STANDARD_DEVIATION 7.0 • n=4 Participants	73.3 years STANDARD_DEVIATION 6.8 • n=27 Participants
Age, Customized 50 to < 60 years	2 participants n=93 Participants	2 participants n=4 Participants	4 participants n=27 Participants
Age, Customized 60 to < 70 years	10 participants n=93 Participants	11 participants n=4 Participants	21 participants n=27 Participants
Age, Customized 70 to < 80 years	30 participants n=93 Participants	31 participants n=4 Participants	61 participants n=27 Participants
Age, Customized 80 to < 90 years	10 participants n=93 Participants	7 participants n=4 Participants	17 participants n=27 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Sex: Female, Male Male	52 Participants n=93 Participants	51 Participants n=4 Participants	103 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) White	52 Participants n=93 Participants	51 Participants n=4 Participants	103 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Karnofsky index (%) 100%	21 participants n=93 Participants	27 participants n=4 Participants	48 participants n=27 Participants
Karnofsky index (%) 90%	18 participants n=93 Participants	12 participants n=4 Participants	30 participants n=27 Participants
Karnofsky index (%) 80%	13 participants n=93 Participants	12 participants n=4 Participants	25 participants n=27 Participants
Prostate specific antigen (PSA) level	47.1 ng/mL STANDARD_DEVIATION 174.9 • n=93 Participants	97.2 ng/mL STANDARD_DEVIATION 368.0 • n=4 Participants	71.7 ng/mL STANDARD_DEVIATION 286.0 • n=27 Participants
Testosterone serum level	3.23 ng/mL STANDARD_DEVIATION 1.28 • n=93 Participants	3.12 ng/mL STANDARD_DEVIATION 1.36 • n=4 Participants	3.18 ng/mL STANDARD_DEVIATION 1.31 • n=27 Participants
Tumour-related pain	0.25 cm STANDARD_DEVIATION 0.58 • n=93 Participants	0.37 cm STANDARD_DEVIATION 0.99 • n=4 Participants	0.31 cm STANDARD_DEVIATION 0.81 • n=27 Participants

PRIMARY outcome

Timeframe: 1, 3, 5, 8, 15, 22, 29, 57, 85 days post-dose

Population: Analysed from ITT population.

Outcome measures

Outcome measures
Measure	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. n=52 Participants Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85.	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM. n=51 Participants Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85.
Area Under the Curve of Testosterone Serum Concentration Between D1 and D85 (AUC1-85d).	4.24 log(ng*day/mL) Standard Deviation 0.40	4.23 log(ng*day/mL) Standard Deviation 0.50

SECONDARY outcome

Timeframe: 1, 3, 5, 8, 15, 22, 29, 57, 85, 87, 113, 141 and 169 days post-dose

Area under the curve calculated from serum testosterone concentration taken at intervals between the first administration (Day 1) of the study drug and Day 169 after dosing. From the curve describing serum testosterone concentration levels (ng/mL) over time, the AUC was calculated using numerical integration methods. This value was log-transformed to more closely meet the assumption of the statistical method.

Outcome measures

Outcome measures
Measure	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. n=52 Participants Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85.	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM. n=51 Participants Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85.
Area Under the Curve of Testosterone Serum Concentration Between D1 and D169 (AUC1-169d)	4.49 log(ng*day/mL) Standard Deviation 0.42	4.52 log(ng*day/mL) Standard Deviation 0.56

SECONDARY outcome

Timeframe: 85, 87, 113, 141 and 169 days post-dose

Population: 95 patients (IM: 47 patients, SC: 48 patients) received a second injection of the study drug.

Area under the curve calculated from serum testosterone concentration taken at intervals between Day 85 and Day 169 after dosing. From the curve describing serum testosterone concentration levels (ng/mL) over time, the AUC was calculated using numerical integration methods. This value was log-transformed to more closely meet the assumption of the statistical method.

Outcome measures

Outcome measures
Measure	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. n=48 Participants Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85.	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM. n=47 Participants Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85.
Area Under the Curve of Testosterone Serum Concentration Between D85 and D169 (AUC85-169d)	2.80 log(ng*day/mL) Standard Deviation 0.45	2.88 log(ng*day/mL) Standard Deviation 0.38

SECONDARY outcome

Timeframe: 1, 3, 5, 8, 15, 22, 29, 57, 85, 87, 113, 141 and 169 days post-dose

Population: Analysed for intent-to-treat (ITT) population comprised of 103 patients (IM: 51 and SC: 52 patients).

Cmax was assessed as the maximum testosterone serum concentration between the first administration of the study drug and Day 169.

Outcome measures

Outcome measures
Measure	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. n=52 Participants Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85.	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM. n=51 Participants Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85.
Maximum Concentration of Serum Testosterone [Cmax] - Raw Data	5.74 ng/mL Standard Deviation 2.33	5.50 ng/mL Standard Deviation 2.35

SECONDARY outcome

Timeframe: 1, 3, 5, 8, 15, 22, 29, 57, 85, 87, 113, 141 and 169 days post-dose

Population: Analysed for intent-to-treat (ITT) population comprised of 103 patients (IM: 51 and SC: 52 patients).

Cmax was assessed as the maximum testosterone serum concentration between the first administration of the study drug and Day 169.

Outcome measures

Outcome measures
Measure	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. n=52 Participants Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85.	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM. n=51 Participants Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85.
Maximum Concentration of Serum Testosterone [Cmax] - Log-transformed Data	1.67 log(ng/mL) Standard Deviation 0.42	1.62 log(ng/mL) Standard Deviation 0.42

SECONDARY outcome

Timeframe: 12 weeks

Population: Analysed for intent-to-treat (ITT) population comprised of 103 patients (IM: 51 and SC: 52 patients).

tcast is the number of days between day of first administration of the study drug and the day the testosterone level reaches the limit of castration defined as testosterone level less than or equal to 0.5 ng/mL for the first time. Analysis of tcast was based on the Kaplan-Meier estimator.

Outcome measures

Outcome measures
Measure	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. n=52 Participants Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85.	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM. n=51 Participants Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85.
Time to Castration [Tcast] - Testosterone Level Less Than or Equal to 0.5 ng/mL	22.0 days Interval 22.0 to 23.0	22.0 days Interval 22.0 to 23.0

SECONDARY outcome

Timeframe: 12 weeks

Population: Analysed for intent-to-treat (ITT) population comprised of 103 patients (IM: 51 and SC: 52 patients).

tcast is the number of days between day of first administration of the study drug and the day the testosterone level reaches the limit of castration defined as testosterone level less than 0.5 ng/mL for the first time. Analysis of tcast was based on the Kaplan-Meier estimator.

Outcome measures

Outcome measures
Measure	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. n=52 Participants Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85.	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM. n=51 Participants Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85.
Time to Castration [Tcast] - Testosterone Level Less Than 0.5 ng/mL	22.0 days Interval 22.0 to 23.0	22.0 days Interval 22.0 to 23.0

Adverse Events

Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC.

Serious events: 11 serious events

Other events: 32 other events

Deaths: 0 deaths

Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM.

Serious events: 7 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. n=52 participants at risk Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85.	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM. n=51 participants at risk Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85.
Musculoskeletal and connective tissue disorders Arthralgia	5.8% 3/52 • Number of events 3 • Throughout the treatment period: 169 days.	2.0% 1/51 • Number of events 1 • Throughout the treatment period: 169 days.
General disorders Fatigue	0.00% 0/52 • Throughout the treatment period: 169 days.	5.9% 3/51 • Number of events 3 • Throughout the treatment period: 169 days.
Vascular disorders Hot flush	28.8% 15/52 • Number of events 15 • Throughout the treatment period: 169 days.	27.5% 14/51 • Number of events 14 • Throughout the treatment period: 169 days.
Skin and subcutaneous tissue disorders Hyperhidrosis	9.6% 5/52 • Number of events 5 • Throughout the treatment period: 169 days.	7.8% 4/51 • Number of events 4 • Throughout the treatment period: 169 days.
Renal and urinary disorders Nocturia	5.8% 3/52 • Number of events 3 • Throughout the treatment period: 169 days.	0.00% 0/51 • Throughout the treatment period: 169 days.
Infections and infestations Urinary tract infection	5.8% 3/52 • Number of events 3 • Throughout the treatment period: 169 days.	5.9% 3/51 • Number of events 3 • Throughout the treatment period: 169 days.
Psychiatric disorders Sleep disorder	5.8% 3/52 • Number of events 3 • Throughout the treatment period: 169 days.	0.00% 0/51 • Throughout the treatment period: 169 days.

Additional Information

Director, Uro-oncology

Ipsen

Phone: [email protected]

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. n=52 participants at risk Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85.	Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM. n=51 participants at risk Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85.
Cardiac disorders Angina pectoris	1.9% 1/52 • Number of events 1 • Throughout the treatment period: 169 days.	0.00% 0/51 • Throughout the treatment period: 169 days.
Renal and urinary disorders Bladder outlet obstruction	0.00% 0/52 • Throughout the treatment period: 169 days.	2.0% 1/51 • Number of events 1 • Throughout the treatment period: 169 days.
Infections and infestations Bronchitis	1.9% 1/52 • Number of events 1 • Throughout the treatment period: 169 days.	0.00% 0/51 • Throughout the treatment period: 169 days.
Infections and infestations Cellulitis	1.9% 1/52 • Number of events 1 • Throughout the treatment period: 169 days.	0.00% 0/51 • Throughout the treatment period: 169 days.
Nervous system disorders Cerebrovascular accident	1.9% 1/52 • Number of events 1 • Throughout the treatment period: 169 days.	0.00% 0/51 • Throughout the treatment period: 169 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	1.9% 1/52 • Number of events 1 • Throughout the treatment period: 169 days.	0.00% 0/51 • Throughout the treatment period: 169 days.
Cardiac disorders Coronary artery disease	1.9% 1/52 • Number of events 1 • Throughout the treatment period: 169 days.	0.00% 0/51 • Throughout the treatment period: 169 days.
Cardiac disorders Coronary artery stenosis	1.9% 1/52 • Number of events 1 • Throughout the treatment period: 169 days.	0.00% 0/51 • Throughout the treatment period: 169 days.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.9% 1/52 • Number of events 1 • Throughout the treatment period: 169 days.	0.00% 0/51 • Throughout the treatment period: 169 days.
Renal and urinary disorders Haematuria	1.9% 1/52 • Number of events 1 • Throughout the treatment period: 169 days.	0.00% 0/51 • Throughout the treatment period: 169 days.
Vascular disorders Hypertension	0.00% 0/52 • Throughout the treatment period: 169 days.	2.0% 1/51 • Number of events 1 • Throughout the treatment period: 169 days.
Gastrointestinal disorders Inguinal hernia	1.9% 1/52 • Number of events 1 • Throughout the treatment period: 169 days.	0.00% 0/51 • Throughout the treatment period: 169 days.
Gastrointestinal disorders Inguinal hernia, obstructive	1.9% 1/52 • Number of events 1 • Throughout the treatment period: 169 days.	2.0% 1/51 • Number of events 1 • Throughout the treatment period: 169 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	1.9% 1/52 • Number of events 1 • Throughout the treatment period: 169 days.	0.00% 0/51 • Throughout the treatment period: 169 days.
Infections and infestations Mediastinitis	1.9% 1/52 • Number of events 1 • Throughout the treatment period: 169 days.	0.00% 0/51 • Throughout the treatment period: 169 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastasis	1.9% 1/52 • Number of events 1 • Throughout the treatment period: 169 days.	0.00% 0/51 • Throughout the treatment period: 169 days.
Infections and infestations Peritonitis	1.9% 1/52 • Number of events 1 • Throughout the treatment period: 169 days.	0.00% 0/51 • Throughout the treatment period: 169 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasmacytoma	0.00% 0/52 • Throughout the treatment period: 169 days.	2.0% 1/51 • Number of events 1 • Throughout the treatment period: 169 days.
Renal and urinary disorders Pyuria	0.00% 0/52 • Throughout the treatment period: 169 days.	2.0% 1/51 • Number of events 1 • Throughout the treatment period: 169 days.
Infections and infestations Rectal abscess	0.00% 0/52 • Throughout the treatment period: 169 days.	2.0% 1/51 • Number of events 1 • Throughout the treatment period: 169 days.
Renal and urinary disorders Renal failure	1.9% 1/52 • Number of events 1 • Throughout the treatment period: 169 days.	0.00% 0/51 • Throughout the treatment period: 169 days.
Renal and urinary disorders Renal failure acute	0.00% 0/52 • Throughout the treatment period: 169 days.	2.0% 1/51 • Number of events 1 • Throughout the treatment period: 169 days.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	1.9% 1/52 • Number of events 1 • Throughout the treatment period: 169 days.	0.00% 0/51 • Throughout the treatment period: 169 days.
Infections and infestations Sepsis	1.9% 1/52 • Number of events 1 • Throughout the treatment period: 169 days.	0.00% 0/51 • Throughout the treatment period: 169 days.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/52 • Throughout the treatment period: 169 days.	2.0% 1/51 • Number of events 1 • Throughout the treatment period: 169 days.
Nervous system disorders Transient ischaemic attack	0.00% 0/52 • Throughout the treatment period: 169 days.	2.0% 1/51 • Number of events 1 • Throughout the treatment period: 169 days.
Gastrointestinal disorders Umbilical hernia	1.9% 1/52 • Number of events 1 • Throughout the treatment period: 169 days.	0.00% 0/51 • Throughout the treatment period: 169 days.
Renal and urinary disorders Urethral stenosis	0.00% 0/52 • Throughout the treatment period: 169 days.	2.0% 1/51 • Number of events 1 • Throughout the treatment period: 169 days.
Renal and urinary disorders Urinary retention	1.9% 1/52 • Number of events 1 • Throughout the treatment period: 169 days.	0.00% 0/51 • Throughout the treatment period: 169 days.
Infections and infestations Urosepsis	1.9% 1/52 • Number of events 1 • Throughout the treatment period: 169 days.	2.0% 1/51 • Number of events 1 • Throughout the treatment period: 169 days.
Gastrointestinal disorders Vomiting	1.9% 1/52 • Number of events 1 • Throughout the treatment period: 169 days.	0.00% 0/51 • Throughout the treatment period: 169 days.