Lanreotide as Primary Treatment for Acromegalic Patients With Pituitary Gland Macroadenoma (PRIMARYS)

• ClinicalTrials.gov Identifier: NCT00690898
• Recruitment Status: Completed
• First Posted: June 5, 2008
• Results First Posted: December 23, 2013
• Last Update Posted: October 14, 2022
• Sponsor: Ipsen
• Information provided by (Responsible Party): Ipsen

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Acromegaly
• Intervention: Drug: Lanreotide autogel 120 mg
• Enrollment: 108

Participant Flow

Recruitment Details	Newly diagnosed acromegaly patients with pituitary tumour were recruited at 27 investigational sites in 9 countries namely Belgium, Finland, France, Czech Republic, Germany, Italy, the Netherlands, Turkey and the United Kingdom.
Pre-assignment Details

Arm/Group Title	Lanreotide Autogel 120 mg
Arm/Group Description	One Lanreotide Autogel subcutaneous (s.c.) injection administered every 28 days for 12 courses as primary medical treatment in newly diagnosed acromegaly patients with pituitary tumour.
Period Title: SCREENING
Started	108 [1]
Completed	90 [2]
Not Completed	18
Reason Not Completed
Screen failure	18
[1] Total of patients screened for the study.; [2] Number of patients included in the study.
Period Title: TREATMENT
Started	90 [1]
Completed	64
Not Completed	26
Reason Not Completed
Adverse Event	3
Lack of Efficacy	18
Withdrawal by Subject	4
Other (not otherwise specified)	1
[1] Total number of patients treated.

Baseline Characteristics

Arm/Group Title		Lanreotide Autogel 120 mg
Arm/Group Description		One Lanreotide Autogel subcutaneous (s.c.) injection administered every 28 days for 12 courses as primary medical treatment in newly diagnosed acromegaly patients with pituitary tumour.
Overall Number of Baseline Participants		90
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	90 participants
		49.5 (12.4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	90 participants
	Female	47 52.2%
	Male	43 47.8%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	90 participants
France		42
United Kingdom		17
Germany		10
Italy		7
Netherlands		4
Czech Republic		3
Finland		3
Belgium		2
Turkey		2
Maximum pituitary adenoma diameter (V1); Mean (Standard Deviation); Unit of measure: Mm
	Number Analyzed	90 participants
		19.0 (7.1)
Acromegaly Symptoms [1]; Mean (Standard Deviation); Unit of measure: Score on a scale	Number Analyzed	90 participants
Headache		2.8 (2.6)
Excessive perspiration		4.1 (2.4)
Fatigue		4.2 (2.5)
Soft tissue swelling		4.1 (2.4)
Arthralgia		3.5 (2.6)
		[1] Measure Description: Acromegaly symptoms assessed on a scale of 0 to 8 (0- no symptoms to 8-severe/incapacitating).
Time since acromegaly diagnosis; Mean (Standard Deviation); Unit of measure: Days
	Number Analyzed	90 participants
		121.2 (149.9)
Pituitary gland MRI volume (V1); Mean (Standard Deviation); Unit of measure: Mm^3
	Number Analyzed	90 participants
		2739.3 (3262.7)
Growth Hormone (GH) level; Mean (Standard Deviation); Unit of measure: mcg/L
	Number Analyzed	90 participants
		15.0 (18.8)
Insulin-like Growth Factor 1 (IGF-1) level; Mean (Standard Deviation); Unit of measure: mcg/L
	Number Analyzed	90 participants
		810 (300)
Prolactin level; Mean (Standard Deviation); Unit of measure: mcg/L
	Number Analyzed	90 participants
		19.0 (20.2)
Global AcroQoL score [1]; Mean (Standard Deviation); Unit of measure: Score on a scale
	Number Analyzed	90 participants
		56.4 (16.1)
		[1] Measure Description: Acromegaly Quality of Life Assessment (AcroQoL) questionnaire response scores range from 0 to 100. Higher scores indicate best possible Quality of Life. AcroQoL not assessed in patients from Turkey and Finland.

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With Relevant Reduction in Pituitary Tumour Volume (as Measured by MRI) From Baseline Volume (Visit 1) to Week 48 (After 12 Injections at Visit 5)
Description	A blinded, centrally assessed evaluation of all MRIs was performed. A 20% reduction from the volume at Visit 1 was considered to be clinically relevant.
Time Frame	Week 1 and Week 48

Outcome Measure Data

Analysis Population Description

Analysis based on intent-to-treat (ITT) population comprised of 89 patients.

Arm/Group Title	Lanreotide Autogel 120 mg
Arm/Group Description:	One Lanreotide Autogel subcutaneous (s.c.) injection administered every 28 days for 12 courses as primary medical treatment in newly diagnosed acromegaly patients with pituitary tumour.
Overall Number of Participants Analyzed	89
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of subjects
Greater than or equal to 20%	62.9; (52.0 to 72.9)
Less than 20%	37.1; (27.1 to 48.0)

2. Secondary Outcome

Title	Number of Patients With at Least a 20% Reduction in Tumour Volume From Baseline Volume (Visit 1) to Week 12 (Visit 3) and Week 24 (Visit 4).
Description	[Not Specified]
Time Frame	Baseline (week 1) to week 12 and week 24

Outcome Measure Data

Analysis Population Description

Analysis based on number (n) of subjects in the Intent to Treat population (ITT) with a valid value.

Arm/Group Title	Lanreotide Autogel 120 mg
Arm/Group Description:	One Lanreotide Autogel subcutaneous (s.c.) injection administered every 28 days for 12 courses as primary medical treatment in newly diagnosed acromegaly patients with pituitary tumour.
Overall Number of Participants Analyzed	89
Measure Type: Number; Unit of Measure: participants
Greater than or equal to 20% at week 12 (n=85)	46
Less than 20% at week 12 (n=85)	39
Greater than or equal to 20% at week 24 (n=80)	45
Less than 20% at week 24 (n=80)	35

3. Secondary Outcome

Title	Percent Variation From Baseline to Visit 3, 4 and 5 (Week 12, 24, and 48) of IGF-1 Levels
Description	[Not Specified]
Time Frame	Week 12, 24, and 48

Outcome Measure Data

Analysis Population Description

Analysis based on number (n) of patients with a valid value in the intent-to-treat (ITT) population.

Arm/Group Title	Lanreotide Autogel 120 mg
Arm/Group Description:	One Lanreotide Autogel subcutaneous (s.c.) injection administered every 28 days for 12 courses as primary medical treatment in newly diagnosed acromegaly patients with pituitary tumour.
Overall Number of Participants Analyzed	89
Mean (95% Confidence Interval); Unit of Measure: percentage change
Week 12 (n=85)	-43.8; (-50.1 to -37.5)
Week 24 (n=78)	-47.4; (-53.6 to -41.2)
Week 48 (n=62)	-56.7; (-62.1 to -51.3)

4. Secondary Outcome

Title	Percent Variation From Baseline to Visit 3, 4 and 5 (Week 12, 24, and 48) of Serum GH Levels.
Description	[Not Specified]
Time Frame	Week 12, 24, and 48

Outcome Measure Data

Analysis Population Description

Analysis based on number (n) of subjects in the Intent to Treat population (ITT) with a valid value.

Arm/Group Title	Lanreotide Autogel 120 mg
Arm/Group Description:	One Lanreotide Autogel subcutaneous (s.c.) injection administered every 28 days for 12 courses as primary medical treatment in newly diagnosed acromegaly patients with pituitary tumour.
Overall Number of Participants Analyzed	85
Mean (95% Confidence Interval); Unit of Measure: percentage change
Week 12 (n=85)	-62.1; (-70.5 to -53.6)
Week 24 (n=78)	-64.6; (-72.3 to -57.0)
Week 48 (n=63)	-70.9; (-79.2 to -62.5)

5. Secondary Outcome

Title	Change From Baseline to Visit 3, 4 and 5 (Week 12, 24, and 48) of Prolactin Levels
Description	[Not Specified]
Time Frame	Week 12, 24 and 48

Outcome Measure Data

Analysis Population Description

Analysis based on the number (n) of subjects with baseline level between 20 ng/ml and 100 ng/ml in the ITT population with a valid value.

Arm/Group Title	Lanreotide Autogel 120 mg
Arm/Group Description:	One Lanreotide Autogel subcutaneous (s.c.) injection administered every 28 days for 12 courses as primary medical treatment in newly diagnosed acromegaly patients with pituitary tumour.
Overall Number of Participants Analyzed	21
Mean (Standard Deviation); Unit of Measure: mcg/L
Prolactin levels at baseline (n=21)	48.0 (24.4)
Change From Baseline to Week 12 (n=20)	-18.0 (19.0)
Change From Baseline to Week 24 (n=20)	-18.6 (20.3)
Change From Baseline to Week 48 (n=12)	-17.3 (18.4)

6. Secondary Outcome

Title	Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Arthralgia) From Baseline
Description	The status of clinical signs of acromegaly assessed by an acromegaly symptoms questionnaire (paper form) completed by the patient at each study visit. The scoring for each clinical sign of acromegaly on the questionnaire is from 0 (no symptom) to 8 (severe, incapacitating symptom). The variation (or no variation) in scores indicate whether the clinical sign of acromegaly had improved, worsened or was unchanged.
Time Frame	Week 12, 24 and 48

Outcome Measure Data

Analysis Population Description

Analysis based on the number (n) of subjects in the ITT population with a valid value.

Arm/Group Title	Lanreotide Autogel 120 mg
Arm/Group Description:	One Lanreotide Autogel subcutaneous (s.c.) injection administered every 28 days for 12 courses as primary medical treatment in newly diagnosed acromegaly patients with pituitary tumour.
Overall Number of Participants Analyzed	89
Measure Type: Number; Unit of Measure: percentage of subjects
Baseline to week 12 - Worsened (n=88)	9.1
Baseline to week 12 - Unchanged (n=88)	26.1
Baseline to week 12 - Improved (n=88)	64.8
Baseline to week 24 - Worsened (n=81)	11.1
Baseline to week 24 - Unchanged (n=81)	24.7
Baseline to week 24 - Improved (n=81)	64.2
Baseline to week 48 - Worsened (n=62)	17.7
Baseline to week 48 - Unchanged (n=62)	22.6
Baseline to week 48 - Improved (n=62)	59.7

7. Secondary Outcome

Title	Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Excessive Perspiration) From Baseline
Description	The status of clinical signs of acromegaly assessed by an acromegaly symptoms questionnaire (paper form) completed by the patient at each study visit. The scoring for each clinical sign of acromegaly on the questionnaire is from 0 (no symptom) to 8 (severe, incapacitating symptom). The variation (or no variation) in scores indicate whether the clinical sign of acromegaly had improved, worsened or was unchanged.
Time Frame	Week 12, 24 and 48

Outcome Measure Data

Analysis Population Description

Analysis based on the number (n) of subjects in the ITT population with a valid value.

Arm/Group Title	Lanreotide Autogel 120 mg
Arm/Group Description:	One Lanreotide Autogel subcutaneous (s.c.) injection administered every 28 days for 12 courses as primary medical treatment in newly diagnosed acromegaly patients with pituitary tumour.
Overall Number of Participants Analyzed	88
Measure Type: Number; Unit of Measure: percentage of subjects
Baseline to week 12 - Worsened (n=88)	11.4
Baseline to week 12 - Unchanged (n=88)	25.0
Baseline to week 12 - Improved (n=88)	63.6
Baseline to week 24 - Worsened (n=81)	14.8
Baseline to week 24 - Unchanged (n=81)	21.0
Baseline to week 24 - Improved (n=81)	64.2
Baseline to week 48 - Worsened (n=62)	9.7
Baseline to week 48 - Unchanged (n=62)	24.2
Baseline to week 48 - Improved (n=62)	66.1

8. Secondary Outcome

Title	Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Fatigue) From Baseline
Description	The status of clinical signs of acromegaly assessed by an acromegaly symptoms questionnaire (paper form) completed by the patient at each study visit. The scoring for each clinical sign of acromegaly on the questionnaire is from 0 (no symptom) to 8 (severe, incapacitating symptom). The variation (or no variation) in scores indicate whether the clinical sign of acromegaly had improved, worsened or was unchanged.
Time Frame	Week 12, 24 and 48

Outcome Measure Data

Analysis Population Description

Analysis based on the number (n) of subjects in the ITT population with a valid value.

Arm/Group Title	Lanreotide Autogel 120 mg
Arm/Group Description:	One Lanreotide Autogel subcutaneous (s.c.) injection administered every 28 days for 12 courses as primary medical treatment in newly diagnosed acromegaly patients with pituitary tumour.
Overall Number of Participants Analyzed	88
Measure Type: Number; Unit of Measure: percentage of subjects
Baseline to week 12 - Worsened (n=88)	13.6
Baseline to week 12 - Unchanged (n=88)	25.0
Baseline to week 12 - Improved (n=88)	61.4
Baseline to week 24 - Worsened (n=81)	16.0
Baseline to week 24 - Unchanged (n=81)	17.3
Baseline to week 24 - Improved (n=81)	66.7
Baseline to week 48 - Worsened (n=62)	14.5
Baseline to week 48 - Unchanged (n=62)	29.0
Baseline to week 48 - Improved (n=62)	56.5

9. Secondary Outcome

Title	Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Headache) From Baseline
Description	The status of clinical signs of acromegaly assessed by an acromegaly symptoms questionnaire (paper form) completed by the patient at each study visit. The scoring for each clinical sign of acromegaly on the questionnaire is from 0 (no symptom) to 8 (severe, incapacitating symptom). The variation (or no variation) in scores indicate whether the clinical sign of acromegaly had improved, worsened or was unchanged.
Time Frame	Week 12, 24 and 48

Outcome Measure Data

Analysis Population Description

Analysis based on the number (n) of subjects in the ITT population with a valid value.

Arm/Group Title	Lanreotide Autogel 120 mg
Arm/Group Description:	One Lanreotide Autogel subcutaneous (s.c.) injection administered every 28 days for 12 courses as primary medical treatment in newly diagnosed acromegaly patients with pituitary tumour.
Overall Number of Participants Analyzed	88
Measure Type: Number; Unit of Measure: percentage of subjects
Baseline to week 12 - Worsened (n=88)	13.6
Baseline to week 12 - Unchanged (n=88)	46.6
Baseline to week 12 - Improved (n=88)	39.8
Baseline to week 24 - Worsened (n=81)	11.1
Baseline to week 24 - Unchanged (n=81)	42.0
Baseline to week 24 - Improved (n=81)	46.9
Baseline to week 48 - Worsened (n=62)	14.5
Baseline to week 48 - Unchanged (n=62)	46.8
Baseline to week 48 - Improved (n=62)	38.7

10. Secondary Outcome

Title	Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Soft Tissue Swelling) From Baseline
Description	The status of clinical signs of acromegaly assessed by an acromegaly symptoms questionnaire (paper form) completed by the patient at each study visit. The scoring for each clinical sign of acromegaly on the questionnaire is from 0 (no symptom) to 8 (severe, incapacitating symptom). The variation (or no variation) in scores indicate whether the clinical sign of acromegaly had improved, worsened or was unchanged.
Time Frame	Week 12, 24 and 48

Outcome Measure Data

Analysis Population Description

Analysis based on the number (n) of subjects in the ITT population with a valid value.

Arm/Group Title	Lanreotide Autogel 120 mg
Arm/Group Description:	One Lanreotide Autogel subcutaneous (s.c.) injection administered every 28 days for 12 courses as primary medical treatment in newly diagnosed acromegaly patients with pituitary tumour.
Overall Number of Participants Analyzed	88
Measure Type: Number; Unit of Measure: percentage of subjects
Baseline to week 12 - Worsened (n=88)	10.2
Baseline to week 12 - Unchanged (n=88)	26.1
Baseline to week 12 - Improved (n=88)	63.6
Baseline to week 24 - Worsened (n=81)	11.1
Baseline to week 24 - Unchanged (n=81)	22.2
Baseline to week 24 - Improved (n=81)	66.7
Baseline to week 48 - Worsened (n=62)	14.5
Baseline to week 48 - Unchanged (n=62)	19.4
Baseline to week 48 - Improved (n=62)	66.1

11. Secondary Outcome

Title	Changes in the Global Acromegaly Quality of Life Assessment (AcroQoL) From Baseline
Description	Acromegaly Quality of Life Assessment (AcroQoL) questionnaire response scores range from 0 to 100. Higher scores indicate best possible Quality of Life.
Time Frame	Week 12, 24 and 48

Outcome Measure Data

Analysis Population Description

Analysis based on the number (n) of subjects in the ITT population with a valid value.

Arm/Group Title	Lanreotide Autogel 120 mg
Arm/Group Description:	One Lanreotide Autogel subcutaneous (s.c.) injection administered every 28 days for 12 courses as primary medical treatment in newly diagnosed acromegaly patients with pituitary tumour.
Overall Number of Participants Analyzed	84
Mean (95% Confidence Interval); Unit of Measure: units on a scale
Baseline to week 12 (n=82)	7.8; (5.7 to 9.8)
Baseline to week 24 (n=75)	8.0; (5.3 to 10.8)
Baseline to week 48 (n=59)	9.5; (6.2 to 12.8)

Adverse Events

Time Frame	Four years
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Lanreotide Autogel 120 mg
Arm/Group Description	One Lanreotide Autogel subcutaneous (s.c.) injection administered every 28 days for 12 courses as primary medical treatment in newly diagnosed acromegaly patients with pituitary tumour.
All-Cause Mortality
	Lanreotide Autogel 120 mg
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Lanreotide Autogel 120 mg
	Affected / at Risk (%)	# Events
Total	13/90 (14.44%)
Blood and lymphatic system disorders
Anaemia * 1	1/90 (1.11%)	1
Endocrine disorders
Hyperparathyroidism * 1	1/90 (1.11%)	1
Eye disorders
Visual acuity reduced * 1	1/90 (1.11%)	1
Gastrointestinal disorders
Pneumoperitoneum * 1	1/90 (1.11%)	1
General disorders
Hypothermia * 1	1/90 (1.11%)	1
Investigations
Gamma-glutamyltransferase increased * 1	1/90 (1.11%)	1
Insulin-like growth factor increased * 1	1/90 (1.11%)	1
Oxygen saturation decreased * 1	1/90 (1.11%)	1
Musculoskeletal and connective tissue disorders
Osteoarthritis * 1	1/90 (1.11%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer * 1	1/90 (1.11%)	1
Thyroid neoplasm * 1	1/90 (1.11%)	1
Nervous system disorders
Intracranial hypotension * 1	1/90 (1.11%)	1
Syncope * 1	2/90 (2.22%)	2
Renal and urinary disorders
Renal colic * 1	1/90 (1.11%)	1
Reproductive system and breast disorders
Ovarian cyst * 1	1/90 (1.11%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea * 1	1/90 (1.11%)	1
Epistaxis * 1	1/90 (1.11%)	1
Sleep apnoea syndrome * 1	1/90 (1.11%)	2
Surgical and medical procedures
Hypophysectomy * 1	1/90 (1.11%)	1
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA Version: 13.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Lanreotide Autogel 120 mg
	Affected / at Risk (%)	# Events
Total	72/90 (80.00%)
Gastrointestinal disorders
Abdominal pain * 1	9/90 (10.00%)	16
Diarrhoea * 1	35/90 (38.89%)	98
Gastrointestinal disorder * 1	10/90 (11.11%)	16
Nausea * 1	6/90 (6.67%)	14
General disorders
Fatigue * 1	5/90 (5.56%)	5
Hepatobiliary disorders
Cholelithiasis 6 (6.7%) [7] * 1	6/90 (6.67%)	7
Skin and subcutaneous tissue disorders
Alopecia * 1	12/90 (13.33%)	12
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA Version: 13.1

Limitations and 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.

Results Point of Contact

• Name/Title: Medical Director, Endocrinology
• Organization: Ipsen
• Phone: clinical.trials@ipsen.com
• EMail: clinical.trials@ipsen.com

Publications of Results:

Caron PJ, Bevan JS, Petersenn S, Flanagan D, Tabarin A, Prevost G, Maisonobe P, Clermont A; PRIMARYS Investigators. Tumor shrinkage with lanreotide Autogel 120 mg as primary therapy in acromegaly: results of a prospective multicenter clinical trial. J Clin Endocrinol Metab. 2014 Apr;99(4):1282-90. doi: 10.1210/jc.2013-3318. Epub 2013 Jan 1.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Caron PJ, Bevan JS, Petersenn S, Houchard A, Sert C, Webb SM; PRIMARYS Investigators Group. Effects of lanreotide Autogel primary therapy on symptoms and quality-of-life in acromegaly: data from the PRIMARYS study. Pituitary. 2016 Apr;19(2):149-57. doi: 10.1007/s11102-015-0693-y.

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT00690898
• Obsolete Identifiers: NCT00225134
• Other Study ID Numbers: 2-79-52030-207; 2007-000155-34 ( EudraCT Number )
• First Submitted: June 3, 2008
• First Posted: June 5, 2008
• Results First Submitted: November 4, 2013
• Results First Posted: December 23, 2013
• Last Update Posted: October 14, 2022