A Phase IIa. Open-label, Multicenter, Dose-escalation Study to Assess the Tolerability and Pharmacokinetics of ZD4054 (Zibotentan) Given Orally Once Daily in Subjects With Metastatic Prostate Cancer

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00055471
• Collaborator: (none)
• Enrollment: 22
• Locations: 2
• Arms: 3
• Duration (Months): 28
• Patients Per Site: 11
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The primary purpose of this study is to determine the safest dose of ZD4054 (Zibotentan)in men with prostate cancer

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms; Metastases, Neoplasm	Drug: ZD4054 10 mg; Drug: ZD4054 15 mg; Drug: ZD4054 22.5 mg	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Primary Purpose: Treatment
• Study Start Date: Jun 1, 2003
• Actual Primary Completion Date: Oct 1, 2005
• Actual Study Completion Date: Oct 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ZD4054 10 mg 1 x 10 mg oral tablets once daily	Drug: ZD4054 10 mg; 1 x 10 mg oral tablets once daily; Other Names: Zibotentan,
Experimental: ZD4054 15 mg 1 x 10 mg + 2 x 2.5 mg oral tablets once daily	Drug: ZD4054 15 mg; 1 x 10 mg + 2 x 2.5 mg oral tablets once daily; Other Names: Zibotentan
Experimental: ZD4054 22.5 mg 2 x 10 mg + 1 x 2.5 mg oral tablets once daily	Drug: ZD4054 22.5 mg; 2 x 10 mg + 2 x 2.5 mg oral tablets once daily; Other Names: Zibotentan

Outcome Measures

Primary Outcome Measures

1. Dose Limiting Toxicities (DLTs) [Baseline to Day 29.]

   DLT is defined as experiencing Common Toxicity Criteria (CTC) grade 3 or 4 headache with onset within 24 h of receiving ZD4054, CTC grade 2 rhinitis leading to the withdrawal of the subject, or other CTC grade 3 or 4 toxicity that was considered to be related to ZD4054 treatment. The numbers of patients with a DLT are reported.

Secondary Outcome Measures

1. Total Prostate Specific Antigen (PSA) Concentration [Baseline to Day 15.]

   Total Prostate Specific Antigen (PSA) concentration at Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2).

2. Change in Total Prostate Specific Antigen (PSA) [Baseline to Day 15.]

   Percentage change in total Prostate Specific Antigen (PSA) (ng/mL) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = [(measure at Day 15 - measure at baseline)/measure at baseline]*100

3. Change in Serum Concentration of Bone Alkaline Phosphatase (ALP) [Baseline to Day 15.]

   Percentage change in serum concentration of Bone Alkaline Phosphatase (ALP) (ng/mL) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = [(measure at Day 15 - measure at baseline)/measure at baseline]*100

4. Change in Serum Concentration of Procollagen Type I N Propeptide (PINP) [Baseline to Day 15.]

   Percentage change in serum concentration of Procollagen Type I N Propeptide (PINP) (ng/mL) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = [(measure at Day 15 - measure at baseline)/measure at baseline]*100

5. Change in Serum Concentration of C-Terminal Telopeptide of Type I Collagen (CTx) [Baseline to Day 15.]

   Percentage change in serum concentration of C-Terminal Telopeptide of Type I Collagen (CTx) (ng/mL) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = [(measure at Day 15 - measure at baseline)/measure at baseline]*100

6. Change in Urine Concentration of Type I Collagen-Cross Linked N Telopeptide (NTx) [Baseline to Day 15.]

   Percentage change in urine concentration of Type I Collagen-Cross Linked N Telopeptide (NTx) (nmol BCE/mmol Creatinine) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = [(measure at Day 15 - measure at baseline)/measure at baseline]*100

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Men 18 years & older

• Confirmed diagnosis of prostate cancer with bone metastases

Exclusion Criteria:

• No more than 2 prior chemotherapy regimens

• No radiation, chemotherapy or bisphosphonates in the past 4 weeks

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Cleveland	Ohio	United States	44195
2	Research Site	Madison	Wisconsin	United States

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00055471
• Other Study ID Numbers: 4054IL/0004
• First Posted: Mar 4, 2003
• Last Update Posted: Oct 31, 2012
• Last Verified: Oct 1, 2012

• Keywords provided by AstraZeneca: prostate cancer; Metastatic prostate cancer; bone metastases
• Additional relevant MeSH terms: Prostatic Neoplasms; Neoplasms; Neoplasm Metastasis

Study Results

Participant Flow

Recruitment Details	22 male patients with metastatic prostate cancer and rising Prostate Specific Antigen (PSA) levels were recruited from 11th June 2003 (last subject completed on 31st October 2005). This study was conducted in 2 centres in the United States.
Pre-assignment Detail	6 of the 22 screened patients were not entered into the study as they did not fulfill the study eligibility criteria.

Arm/Group Title	ZD4054 10 mg	ZD4054 15 mg	ZD4054 22.5 mg
Arm/Group Description	ZD4054 10 mg dose: 1 x 10 mg oral tablet once daily	ZD4054 15 mg dose: 1 x 10 mg + 2 x 2.5 mg oral tablets once daily	ZD4054 22.5 mg dose: 2 x 10 mg + 1 x 2.5 mg oral tablets once daily
Period Title: Period 1: Dose Escalation Period
STARTED	3	10	3
COMPLETED	3	8	0
NOT COMPLETED	0	2	3
Period Title: Period 1: Dose Escalation Period
STARTED	3	6	0
COMPLETED	3	6	0
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	ZD4054 10 mg	ZD4054 15 mg	ZD4054 22.5 mg	Total
Arm/Group Description	ZD4054 10 mg dose: 1 x 10 mg oral tablet once daily	ZD4054 15 mg dose: 1 x 10 mg + 2 x 2.5 mg oral tablets once daily	ZD4054 22.5 mg dose: 2 x 10 mg + 1 x 2.5 mg oral tablets once daily	Total of all reporting groups
Overall Participants	3	10	3	16
Age (Years) [Mean (Standard Deviation) ]
Overall	72.3 (3.21)	64.6 (9.72)	66.3 (8.08)	66.4 (8.72)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	3 100%	10 100%	3 100%	16 100%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	3 100%	9 90%	3 100%	15 93.8%
Black	0 0%	1 10%	0 0%	1 6.3%
Oriental	0 0%	0 0%	0 0%	0 0%
Other	0 0%	0 0%	0 0%	0 0%
Height (Centimeters (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Centimeters (cm)]	177.33 (4.51)	177.10 (8.02)	176.33 (5.03)	177 (6.69)
Weight (Kilograms (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilograms (kg)]	87.33 (19.035)	107.8 (21.060)	103.00 (35.595)	103.06 (23.405)

Outcome Measures

1. Primary Outcome

Title	Dose Limiting Toxicities (DLTs)
Description	DLT is defined as experiencing Common Toxicity Criteria (CTC) grade 3 or 4 headache with onset within 24 h of receiving ZD4054, CTC grade 2 rhinitis leading to the withdrawal of the subject, or other CTC grade 3 or 4 toxicity that was considered to be related to ZD4054 treatment. The numbers of patients with a DLT are reported.
Time Frame	Baseline to Day 29.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ZD4054 10 mg	ZD4054 15 mg	ZD4054 22.5 mg
Arm/Group Description	ZD4054 10 mg dose: 1 x 10 mg oral tablet once daily	ZD4054 15 mg dose: 1 x 10 mg + 2 x 2.5 mg oral tablets once daily	ZD4054 22.5 mg dose: 2 x 10 mg + 1 x 2.5 mg oral tablets once daily
Measure Participants	3	10	3
Number [Participants]	0 0%	0 0%	2 66.7%

2. Secondary Outcome

Title	Total Prostate Specific Antigen (PSA) Concentration
Description	Total Prostate Specific Antigen (PSA) concentration at Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2).
Time Frame	Baseline to Day 15.

Outcome Measure Data

Analysis Population Description

All dosed patients.

Arm/Group Title	ZD4054 10 mg	ZD4054 15 mg	ZD4054 22.5 mg
Arm/Group Description	ZD4054 10 mg dose: 1 x 10 mg oral tablet once daily	ZD4054 15 mg dose: 1 x 10 mg + 2 x 2.5 mg oral tablets once daily	ZD4054 22.5 mg dose: 2 x 10 mg + 1 x 2.5 mg oral tablets once daily
Measure Participants	3	10	2
Geometric Mean (Full Range) [ng/ml]	98.454	62.366	56.550

3. Secondary Outcome

Title	Change in Total Prostate Specific Antigen (PSA)
Description	Percentage change in total Prostate Specific Antigen (PSA) (ng/mL) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = [(measure at Day 15 - measure at baseline)/measure at baseline]*100
Time Frame	Baseline to Day 15.

Outcome Measure Data

Analysis Population Description

The analysis population includes only patients dosed with ZD4054

Arm/Group Title	ZD4054 10 mg	ZD4054 15 mg	ZD4054 22.5 mg
Arm/Group Description	ZD4054 10 mg dose: 1 x 10 mg oral tablet once daily	ZD4054 15 mg dose: 1 x 10 mg + 2 x 2.5 mg oral tablets once daily	ZD4054 22.5 mg dose: 2 x 10 mg + 1 x 2.5 mg oral tablets once daily
Measure Participants	3	10	2
Mean (Standard Deviation) [Percentage Change]	2.235 (15.445)	10.986 (21.345)	18.404 (30.132)

4. Secondary Outcome

Title	Change in Serum Concentration of Bone Alkaline Phosphatase (ALP)
Description	Percentage change in serum concentration of Bone Alkaline Phosphatase (ALP) (ng/mL) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = [(measure at Day 15 - measure at baseline)/measure at baseline]*100
Time Frame	Baseline to Day 15.

Outcome Measure Data

Analysis Population Description

The analysis population includes only patients dosed with ZD4054

Arm/Group Title	ZD4054 10 mg	ZD4054 15 mg	ZD4054 22.5 mg
Arm/Group Description	ZD4054 10 mg dose: 1 x 10 mg oral tablet once daily	ZD4054 15 mg dose: 1 x 10 mg + 2 x 2.5 mg oral tablets once daily	ZD4054 22.5 mg dose: 2 x 10 mg + 1 x 2.5 mg oral tablets once daily
Measure Participants	3	10	2
Mean (Standard Deviation) [Percentage Change]	-6.161 (9.616)	-9.197 (12.220)	-9.182 (10.644)

5. Secondary Outcome

Title	Change in Serum Concentration of Procollagen Type I N Propeptide (PINP)
Description	Percentage change in serum concentration of Procollagen Type I N Propeptide (PINP) (ng/mL) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = [(measure at Day 15 - measure at baseline)/measure at baseline]*100
Time Frame	Baseline to Day 15.

Outcome Measure Data

Analysis Population Description

The analysis population includes only patients dosed with ZD4054

Arm/Group Title	ZD4054 10 mg	ZD4054 15 mg	ZD4054 22.5 mg
Arm/Group Description	ZD4054 10 mg dose: 1 x 10 mg oral tablet once daily	ZD4054 15 mg dose: 1 x 10 mg + 2 x 2.5 mg oral tablets once daily	ZD4054 22.5 mg dose: 2 x 10 mg + 1 x 2.5 mg oral tablets once daily
Measure Participants	3	10	2
Mean (Standard Deviation) [Percentage Change]	7.865 (14.625)	20.681 (44.217)	113.012 (51.302)

6. Secondary Outcome

Title	Change in Serum Concentration of C-Terminal Telopeptide of Type I Collagen (CTx)
Description	Percentage change in serum concentration of C-Terminal Telopeptide of Type I Collagen (CTx) (ng/mL) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = [(measure at Day 15 - measure at baseline)/measure at baseline]*100
Time Frame	Baseline to Day 15.

Outcome Measure Data

Analysis Population Description

The analysis population includes only patients dosed with ZD4054

Arm/Group Title	ZD4054 10 mg	ZD4054 15 mg	ZD4054 22.5 mg
Arm/Group Description	ZD4054 10 mg dose: 1 x 10 mg oral tablet once daily	ZD4054 15 mg dose: 1 x 10 mg + 2 x 2.5 mg oral tablets once daily	ZD4054 22.5 mg dose: 2 x 10 mg + 1 x 2.5 mg oral tablets once daily
Measure Participants	3	10	2
Mean (Standard Deviation) [Percentage Change]	-13.832 (19.003)	44.855 (94.876)	20.386 (31.094)

7. Secondary Outcome

Title	Change in Urine Concentration of Type I Collagen-Cross Linked N Telopeptide (NTx)
Description	Percentage change in urine concentration of Type I Collagen-Cross Linked N Telopeptide (NTx) (nmol BCE/mmol Creatinine) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = [(measure at Day 15 - measure at baseline)/measure at baseline]*100
Time Frame	Baseline to Day 15.

Outcome Measure Data

Analysis Population Description

The analysis population includes only patients dosed with ZD4054

Arm/Group Title	ZD4054 10 mg	ZD4054 15 mg	ZD4054 22.5 mg
Arm/Group Description	ZD4054 10 mg dose: 1 x 10 mg oral tablet once daily	ZD4054 15 mg dose: 1 x 10 mg + 2 x 2.5 mg oral tablets once daily	ZD4054 22.5 mg dose: 2 x 10 mg + 1 x 2.5 mg oral tablets once daily
Measure Participants	3	10	2
Mean (Standard Deviation) [Percentage Change]	-25.213 (15.389)	2.154 (41.900)	-5.942 (34.344)

Adverse Events

Arm/Group Title	ZD4054 10 mg		ZD4054 15 mg		ZD4054 22.5 mg
Arm/Group Description	ZD4054 10 mg dose: 1 x 10 mg oral tablet once daily		ZD4054 15 mg dose: 1 x 10 mg + 2 x 2.5 mg oral tablets once daily		ZD4054 22.5 mg dose: 2 x 10 mg + 1 x 2.5 mg oral tablets once daily
All Cause Mortality
	ZD4054 10 mg		ZD4054 15 mg		ZD4054 22.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	ZD4054 10 mg		ZD4054 15 mg		ZD4054 22.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		2/10 (20%)		2/3 (66.7%)
Gastrointestinal disorders
Rectal Haemorrhage	0/3 (0%)		1/10 (10%)		0/3 (0%)
General disorders
Pitting Oedema	0/3 (0%)		1/10 (10%)		0/3 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	0/3 (0%)		1/10 (10%)		0/3 (0%)
Nervous system disorders
Headache	0/3 (0%)		0/10 (0%)		1/3 (33.3%)
Intraventricular Haemorrhage	0/3 (0%)		0/10 (0%)		1/3 (33.3%)
Syncope	0/3 (0%)		0/10 (0%)		1/3 (33.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/3 (0%)		1/10 (10%)		0/3 (0%)
Pleural Effusion	0/3 (0%)		1/10 (10%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	ZD4054 10 mg		ZD4054 15 mg		ZD4054 22.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		10/10 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Anaemia	1/3 (33.3%)		0/10 (0%)		0/3 (0%)
Cardiac disorders
Tachycardia	0/3 (0%)		1/10 (10%)		0/3 (0%)
Ear and labyrinth disorders
Tinnitus	1/3 (33.3%)		0/10 (0%)		0/3 (0%)
Ear Discomfort	0/3 (0%)		1/10 (10%)		0/3 (0%)
Eye disorders
Cataract	1/3 (33.3%)		0/10 (0%)		0/3 (0%)
Lacrimation Increased	0/3 (0%)		1/10 (10%)		0/3 (0%)
Photophobia	0/3 (0%)		1/10 (10%)		0/3 (0%)
Gastrointestinal disorders
Constipation	1/3 (33.3%)		0/10 (0%)		0/3 (0%)
Nausea	1/3 (33.3%)		2/10 (20%)		1/3 (33.3%)
Vomiting	1/3 (33.3%)		1/10 (10%)		1/3 (33.3%)
Abdominal Distension	0/3 (0%)		1/10 (10%)		0/3 (0%)
Abdominal Pain	0/3 (0%)		0/10 (0%)		1/3 (33.3%)
Diarrhoea	0/3 (0%)		3/10 (30%)		0/3 (0%)
Dry Mouth	0/3 (0%)		1/10 (10%)		0/3 (0%)
Flatulence	0/3 (0%)		2/10 (20%)		0/3 (0%)
Stomatitis	0/3 (0%)		1/10 (10%)		0/3 (0%)
Tongue Discolouration	0/3 (0%)		1/10 (10%)		0/3 (0%)
General disorders
Fatigue	0/3 (0%)		4/10 (40%)		3/3 (100%)
Oedema Peripheral	0/3 (0%)		9/10 (90%)		1/3 (33.3%)
Chills	0/3 (0%)		1/10 (10%)		1/3 (33.3%)
Oedema	1/3 (33.3%)		0/10 (0%)		0/3 (0%)
Face Oedema	0/3 (0%)		3/10 (30%)		0/3 (0%)
Infections and infestations
Bronchitis	0/3 (0%)		1/10 (10%)		0/3 (0%)
Nasopharyngitis	0/3 (0%)		1/10 (10%)		0/3 (0%)
Rhinitis	0/3 (0%)		1/10 (10%)		0/3 (0%)
Injury, poisoning and procedural complications
Animal Bite	0/3 (0%)		1/10 (10%)		0/3 (0%)
Arthropod Sting	0/3 (0%)		0/10 (0%)		1/3 (33.3%)
Barotrauma	0/3 (0%)		1/10 (10%)		0/3 (0%)
Contrast Media Reaction	0/3 (0%)		1/10 (10%)		0/3 (0%)
Joint Sprain	0/3 (0%)		1/10 (10%)		0/3 (0%)
Scratch	0/3 (0%)		0/10 (0%)		1/3 (33.3%)
Weight Increased	0/3 (0%)		1/10 (10%)		1/3 (33.3%)
Weight Decreased	1/3 (33.3%)		1/10 (10%)		0/3 (0%)
Electrocardiogram Qt Corrected Interval Prolonged	0/3 (0%)		0/10 (0%)		1/3 (33.3%)
Haemoglobin Decreased	0/3 (0%)		0/10 (0%)		1/3 (33.3%)
Heart Rate Increased	0/3 (0%)		1/10 (10%)		0/3 (0%)
Metabolism and nutrition disorders
Anorexia	0/3 (0%)		2/10 (20%)		1/3 (33.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/3 (33.3%)		2/10 (20%)		2/3 (66.7%)
Back Pain	1/3 (33.3%)		1/10 (10%)		0/3 (0%)
Pain In Extremity	1/3 (33.3%)		1/10 (10%)		2/3 (66.7%)
Buttock Pain	0/3 (0%)		1/10 (10%)		0/3 (0%)
Groin Pain	0/3 (0%)		0/10 (0%)		1/3 (33.3%)
Nervous system disorders
Headache	2/3 (66.7%)		9/10 (90%)		3/3 (100%)
Dizziness	0/3 (0%)		1/10 (10%)		1/3 (33.3%)
Burning Sensation	1/3 (33.3%)		0/10 (0%)		0/3 (0%)
Dysgeusia	0/3 (0%)		2/10 (20%)		0/3 (0%)
Hypoaesthesia	0/3 (0%)		1/10 (10%)		0/3 (0%)
Neuropathy	0/3 (0%)		0/10 (0%)		1/3 (33.3%)
Paraesthesia	0/3 (0%)		1/10 (10%)		0/3 (0%)
Psychiatric disorders
Insomnia	1/3 (33.3%)		0/10 (0%)		0/3 (0%)
Renal and urinary disorders
Haematuria	0/3 (0%)		2/10 (20%)		0/3 (0%)
Urinary Retention	0/3 (0%)		1/10 (10%)		0/3 (0%)
Reproductive system and breast disorders
Testicular Pain	0/3 (0%)		0/10 (0%)		1/3 (33.3%)
Respiratory, thoracic and mediastinal disorders
Sinus Congestion	0/3 (0%)		2/10 (20%)		2/3 (66.7%)
Dyspnoea	0/3 (0%)		1/10 (10%)		1/3 (33.3%)
Nasal Congestion	1/3 (33.3%)		3/10 (30%)		0/3 (0%)
Dry Throat	0/3 (0%)		2/10 (20%)		0/3 (0%)
Dyspnoea Exertional	0/3 (0%)		1/10 (10%)		0/3 (0%)
Pharyngolaryngeal Pain	0/3 (0%)		1/10 (10%)		0/3 (0%)
Postnasal Drip	0/3 (0%)		1/10 (10%)		0/3 (0%)
Rhinorrhoea	0/3 (0%)		1/10 (10%)		0/3 (0%)
Wheezing	0/3 (0%)		1/10 (10%)		0/3 (0%)
Skin and subcutaneous tissue disorders
Pruritus	0/3 (0%)		1/10 (10%)		1/3 (33.3%)
Hyperhidrosis	0/3 (0%)		0/10 (0%)		1/3 (33.3%)
Periorbital Oedema	0/3 (0%)		2/10 (20%)		0/3 (0%)
Skin Discolouration	0/3 (0%)		1/10 (10%)		0/3 (0%)
Vascular disorders
Flushing	0/3 (0%)		1/10 (10%)		0/3 (0%)
Hypotension	0/3 (0%)		0/10 (0%)		1/3 (33.3%)

Limitations/Caveats

One patient received one dose of 22.5 mg and was dose reduced to 15 mg thereafter. This patient was classified into the 15 mg dose group, except for the single dose pharmacokinetic results (not posted).

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.