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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-001833-42 | EudraCT Number |
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A Phase 2 double-blind, placebo-controlled, randomized withdrawal study is designed to evaluate the safety, efficacy, and pharmacokinetics of paltusotine (formerly CRN00808) in subjects with acromegaly that are responders to octreotide LAR or lanreotide depot.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Paltusotine | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Paltusotine | Drug | Paltusotine, capsules, once daily by mouth |
|
| Measure | Description | Time Frame |
|---|---|---|
| Responder Criteria Was Based on the Mean of Two Consecutive Insulin-like Growth Factor-1 [IGF-1] Measurements ≤ULN at Week 13 | Proportion of subjects who meet responder criteria (based on the mean of two consecutive IGF-1 measurements ≤ upper limit of normal [ULN]) | 13 Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in IGF-1 Levels | Change in IGF-1 levels between RWP Baseline/Week 10 and Week 13 | From Week 10 to Week 13 |
| Change in Growth Hormone (GH) Levels | Change in growth hormone levels between RWP Baseline/Week 8 and Week 13 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ohio State University | Columbus | Ohio | 43210 | United States | ||
| The Research Institute of Dallas |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36792844 | Derived | Martin S, Bender RH, Krasner A, Marmon T, Monahan M, Nelson L. Development and evaluation of the Acromegaly Symptom Diary. J Patient Rep Outcomes. 2023 Feb 15;7(1):15. doi: 10.1186/s41687-023-00541-7. |
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Medically stable male and female participants 18 to 75 years of age, with a confirmed acromegaly diagnosis that was controlled on a stable approved dose of octreotide LAR or lanreotide depot. There had to be documentation available of a pituitary tumour and elevated IGF-1 in the past.
Medically stable male and female subjects 18 to 75 years of age, inclusive, with a confirmed acromegaly diagnosis that was controlled on a stable approved dose of octreotide LAR or lanreotide depot. At a minimum, there had to be documentation available of a pituitary tumour and elevated IGF-1 in the past.
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| ID | Title | Description |
|---|---|---|
| FG000 | Titration Period: Paltusotine, Then Randomized Withdrawal Period: Paltusotine | Titration Period started with the first dose of study drug (10mg all subjects) at V3, approximately 4 weeks after V1b when the last dose of standard acromegaly treatment was administered. Subjects who enrolled in the Titration Period did not receive any depot somatostatin receptor ligands (SRL) injections or other standard acromegaly treatment until study completion or early termination. At V6/W4, the study drug dose was titrated up in a blinded fashion, if the current dose was tolerated by the subject and the IGF-1 value at V4/W2 was >0.9×ULN (upper limit of normal for normal IGF-1 values for a specific age and sex). At V9/W7, the study drug was up-titrated in a blinded fashion if the current dose was tolerated by the subject and the IGF-1 value at V7/W5 was >ULN. Investigator confirmed the subject eligibility for an increase in study drug dose based on tolerability at V5/W3, V6/W4, V8/W6, and V9/W7. If tolerability was confirmed and IGF-1 reader determined that IGF-1 had not met adequate suppression criteria, a blinded blister card containing the appropriate higher dose was assigned at the V6/W4 and/or V9/W7. Dose increases in 10 mg increments were allowed only at V6/W4 (from 10 mg to 20 mg) and V9/W7 (from 10 mg to 20 mg, or from 20 mg to 30 mg) visits. No further up-titration was allowed. The daily dose did not exceed 30 mg. If eligible for randomization, the subject was randomized at V11/W10 in a blinded manner to continue the current dose of paltusotine. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Screening Period: 4-6 Weeks |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 6, 2019 | Aug 22, 2024 |
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| Placebo | Drug | Placebo, capsules, once daily by mouth |
|
| From Week 8 to Week 13 |
| Change in Total ASD Score Between RWP Baseline/Week 10 and Week 13 | Measured by total Acromegaly symptom diary (ASD) score from W10-W13. ASD is a sponsor-developed daily diary to assess important acromegaly symptoms from the patient perspective. It covers 7 symptoms (headache pain, joint pain, sweating, fatigue, weakness in legs, swelling, and numbness or tingling). Patients rate the severity of each experience in the past 24 hours on an 11-point numeric scale that ranges from 0 (no symptom) to 10 (worst symptom). A weekly average ASD score is calculated for each item as the sum of the item responses for a specific item over the course of the study week divided by the number of days on which the item was completed. The weekly average ASD total score is calculated by computing the sum of the weekly average item scores for the 7 items (total range from 0 to 70), where higher score = higher symptom severity. | From Week 10 to Week 13 |
| Dallas |
| Texas |
| 10260 |
| United States |
| CETI - Centro de Estudos em Terapias Inovadoras | Curitiba | Brazil |
| CPQuali Pesquisa Clinica | São Paulo | Brazil |
| General Hospital of Athens "Gennimatas" | Athens | Greece |
| Semmelweis University Faculty of Medicine | Budapest | Hungary |
| University of Pécs Medical School | Pécs | Hungary |
| Endocrine, Diabetes and Research Centre, Wellington Hospital | Wellington | New Zealand |
| The Centre of Postgraduate Medical Education | Warsaw | Poland |
| Clinical Centre Serbia, Clinic for Endocrinology, Diabetes and Metabolic Diseases | Belgrade | Serbia |
| National Institute of Endocrinology and Diabetology | Ľubochňa | Slovakia |
| FG001 | Titration Period: Paltusotine, Then Randomized Withdrawal Period: Placebo | Titration Period started with the first dose of study drug (10 mg for all subjects) at V3, approximately 4 weeks after V1b when the last dose of standard acromegaly treatment was administered. Subjects who enrolled in the Titration Period did not receive any depot somatostatin receptor ligands (SRL) depot injections or other standard acromegaly treatment until study completion or early termination. At V6/W4, the study drug dose was titrated up in a blinded fashion, if the current dose was tolerated by the subject and the IGF-1 value at V4/W2 was >0.9×ULN. Again, at V9/W7, the study drug was up-titrated in a blinded fashion if the current dose was tolerated by the subject and the IGF-1 value at V7/W5 was >ULN. The Investigator confirmed the subject was eligible for an increase in the study drug dose based on tolerability at V5/W3, V6/W4, V8/W6, and V9/W7. If tolerability was confirmed and the IGF-1 reader had determined that IGF-1 had not met adequate suppression criteria, a blinded blister card that contained the appropriate higher dose was assigned at the V6/W4 and/or V9/W7. Dose increases in 10 mg increments were allowed only at the V6/W4 (from 10 mg to 20 mg) and V9/W7 (from 10 mg to 20 mg, or from 20 mg to 30 mg) visits. No further up-titration was allowed. The daily dose did not exceed 30 mg. If determined to be eligible for randomization, the subject was randomized at V11/W10 in a blinded manner and switched to placebo. |
| FG002 | Titration Period: Paltusotine, Then Not Randomized | Titration period proceeded for these subjects in the same manner as other groups. To be eligible for randomization, the subject had to have IGF-1 value ≤ULN at V10/W8 and an Investigator determination at V11/W10 that the subject tolerated the study drug. Subjects who did not meet both criteria were not to be randomized but were to be allowed to stay in the study and continue on a study drug dose that was tolerated until completion of all study visits or until criteria to resume standard acromegaly therapy and discontinuation from the study were met. The dose of study drug used at V9/W7 remained stable through V11/W10 if tolerated. |
| COMPLETED |
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| NOT COMPLETED |
|
| Titration Period: up to 9 Weeks |
|
|
| Randomized Withdrawal: up to 4 Weeks |
|
|
| Follow-up Period: up to 4 Weeks |
|
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The Baseline Analysis Population includes all subjects who received treatment in the titration period. This includes subjects who were randomized in the randomized withdrawal period to receive placebo or continue receiving paltusotine and subjects who were not randomized and continued receiving paltusotine. The primary endpoint is presented for all subjects. Secondary endpoints are presented only for the randomized subjects as the RW baseline was not applicable to the non-randomized subjects.
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| ID | Title | Description |
|---|---|---|
| BG000 | Titration Period: Paltusotine, Then Randomized Withdrawal Period: Paltusotine | During the titration period, the study drug dose was titrated up in a blinded fashion. At randomization for the randomized withdrawal period, these subjects continued to receive paltusotine at the same level as end of the titration period. |
| BG001 | Titration Period: Paltusotine, Then Randomized Withdrawal Period: Placebo | During the titration period, the study drug dose was titrated up in a blinded fashion. At randomization for the randomized withdrawal period, these subjects were switched to placebo. |
| BG002 | Titration Period: Paltusotine, Then Not Randomized | Titration period proceeded for these subjects in the same manner as other groups. To be eligible for randomization, the subject had to have IGF-1 value ≤ULN at V10/W8 and an Investigator determination at V11/W10 that the subject tolerated the study drug. Subjects who did not meet both criteria were not to be randomized but were to be allowed to stay in the study and continue on a study drug dose that was tolerated until completion of all study visits or until criteria to resume standard acromegaly therapy and discontinuation from the study were met. The dose of study drug used at V9/W7 remained stable through V11/W10 if tolerated. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| UGT1A1 Genotype | Blood sample for genotyping was analyzed for randomized subjects only and was collected for the determination of the UGT1A1 genotype. Subjects could opt out of this testing. Subjects are reported by genotype sequence (allele UGT1A1*1/*1, *1/*80, or *80/*80). Individuals who inherit certain polymorphisms in the UGT1A1 gene have reduced enzymatic activity. UGT1A1*1 is associated with normal enzyme activity. UGT1A1*1/*80 is associate with intermediate metabolizer phenotype and UGT1A1*80/*80 is associated with poor metabolizer phenotype | Count of Participants | Participants |
| |||||||||||||||
| UGT1A1 Phenotype | Count of Participants | Participants |
| ||||||||||||||||
| Height | Mean | Standard Deviation | cm |
| |||||||||||||||
| Weight | All demographics and baseline characteristics presented are based on the titration period baseline. | Mean | Standard Deviation | kg |
| ||||||||||||||
| BMI | All demographics and baseline characteristics presented are based on the titration period baseline. | Geometric Mean | Standard Deviation | kg/m2 |
| ||||||||||||||
| Ring Size | Finger size is an objective measure of soft tissue over-growth and is assessed using the US Ring Size Scale. Measurements are assessed on an increasing scale of US ring sizes scored from 1-17 (smallest to largest), with an increase in ring size between consecutive visits representing increased peripheral swelling. Ring sizers (Tool jewelry sizing tools) were provided to the sites, and sites were instructed to use the same hand and finger at each visit. | All demographics and baseline characteristics presented are based on the titration period baseline. | Mean | Standard Deviation | Scores on a Scale |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Responder Criteria Was Based on the Mean of Two Consecutive Insulin-like Growth Factor-1 [IGF-1] Measurements ≤ULN at Week 13 | Proportion of subjects who meet responder criteria (based on the mean of two consecutive IGF-1 measurements ≤ upper limit of normal [ULN]) | The Analysis Population includes all subjects who received treatment in the titration period. This includes subjects who were randomized in the randomized withdrawal period to receive placebo or continue receiving paltusotine and subjects who were not randomized and continued receiving paltusotine. The primary endpoint of the proportion of subjects who met responder criteria (based on the mean of two consecutive IGF-1 measurements ≤ULN) at Week 13 is presented for all subjects. | Posted | Number | 95% Confidence Interval | percentage of responders | 13 Weeks |
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| |||||||||||||||||||||||||||||||
| Secondary | Change in IGF-1 Levels | Change in IGF-1 levels between RWP Baseline/Week 10 and Week 13 | Analysis Population includes all subjects who met protocol pre-specified criteria for randomization into paltusotine/placebo. Per the study design, Randomized Withdrawal Period (RWP) baseline only applies to those subjects who met criteria for randomization. RWP baseline is undefined for non-randomized subjects. Demographics and Baseline Characteristics were reported for all subjects at Titration Period Baseline, but not RWP baseline. | Posted | Mean | Standard Deviation | percent change in IGF1 | From Week 10 to Week 13 |
| |||||||||||||||||||||||||||||||||
| Secondary | Change in Growth Hormone (GH) Levels | Change in growth hormone levels between RWP Baseline/Week 8 and Week 13 | Analysis Population includes all subjects who met protocol pre-specified criteria for randomization into paltusotine/placebo. Per the study design, Randomized Withdrawal Period (RWP) baseline only applies to those subjects who met criteria for randomization. RWP baseline is undefined for non-randomized subjects. Demographics and Baseline Characteristics were reported for all subjects at Titration Period Baseline, but not RWP baseline. | Posted | Mean | Standard Deviation | percent change in GH | From Week 8 to Week 13 |
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| Secondary | Change in Total ASD Score Between RWP Baseline/Week 10 and Week 13 | Measured by total Acromegaly symptom diary (ASD) score from W10-W13. ASD is a sponsor-developed daily diary to assess important acromegaly symptoms from the patient perspective. It covers 7 symptoms (headache pain, joint pain, sweating, fatigue, weakness in legs, swelling, and numbness or tingling). Patients rate the severity of each experience in the past 24 hours on an 11-point numeric scale that ranges from 0 (no symptom) to 10 (worst symptom). A weekly average ASD score is calculated for each item as the sum of the item responses for a specific item over the course of the study week divided by the number of days on which the item was completed. The weekly average ASD total score is calculated by computing the sum of the weekly average item scores for the 7 items (total range from 0 to 70), where higher score = higher symptom severity. | Analysis Population includes all subjects who met protocol pre-specified criteria for randomization into paltusotine/placebo. Per the study design, Randomized Withdrawal Period (RWP) baseline only applies to those subjects who met criteria for randomization. RWP baseline is undefined for non-randomized subjects. Demographics and Baseline Characteristics were reported for all subjects at Titration Period Baseline, but not RWP baseline. | Posted | Mean | Standard Deviation | Total ASD score change -units on a scale | From Week 10 to Week 13 |
|
Duration of participation for each subject after obtaining a signed informed consent was up to 23 weeks.
Safety analysis set: All participants enrolled in the study who received any amount of the study drug. All AEs reported in ≥ 1 subject are presented.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Safety Analysis Set/Titration Period - Paltusotine | All participants who received a dose of Paltusotine during the titration period. | 0 | 13 | 0 | 13 | 8 | 13 |
| EG001 | Randomized Withdrawal Period - Paltusotine | Adverse events reported during the randomised withdrawal period by those receiving Paltusotine treatment | 0 | 3 | 0 | 3 | 3 | 3 |
| EG002 | Randomized Withdrawal Period - Placebo | Adverse events reported during the randomised withdrawal period by those receiving Placebo | 0 | 4 | 0 | 4 | 4 | 4 |
| EG003 | Total Paltusotine | All participants who received a dose of paltusotine. Includes all participants randomized into the RWP, and those not randomized that were allowed to stay in the study and continue dosing at a study drug dose that was tolerated, until the participant completed all study visits. | 0 | 13 | 0 | 13 | 10 | 13 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypertension | Vascular disorders | MedDRA 22.1 | Systematic Assessment |
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| Blood glucose increased | Investigations | MedDRA 22.1 | Systematic Assessment |
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| Blood triglycerides increased | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Sleep apnoea syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
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| Sleep disorder | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Respiratory tract infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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Due to small sample size, a number of exploratory endpoints were defined but not summarised. All primary and secondary endpoints are reported.
The only disclosure restriction on the PI is that PIs cannot publish until the multi-center publication is first published. If no multi-center publication is published within 18 months of the completion date, the PI may publish their results, provided that the Sponsor is given the opportunity to review the proposed publication in advance.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Crinetics Clinical Trials | Crinetics Pharmaceuticals Inc. | +1 858-450-6464 | clinicaltrials@crinetics.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 8, 2020 | Aug 22, 2024 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D000172 | Acromegaly |
| ID | Term |
|---|---|
| D001849 | Bone Diseases, Endocrine |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D006964 | Hyperpituitarism |
| D010900 | Pituitary Diseases |
| D007027 | Hypothalamic Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D004700 | Endocrine System Diseases |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| American Indian or Alaska Native |
|
| Asian |
|
| Black or African American |
|
| Native Hawaiian or Other Pacific Islander |
|
| Other |
|
| *1/*80 |
|
| *80/*80 |
|
| Not reported |
|
| Intermediate Metabolizer |
|
| Poor Metabolizer |
|
| Not reported |
|
| OG002 | Randomized Withdrawal Period: Not Randomized | To be eligible for randomization, the subject had to have IGF-1 value ≤ULN at V10/W8 and an Investigator determination at V11/W10 that the subject tolerated the study drug. Subjects who did not meet both criteria were not to be randomized but were to be allowed to stay in the study and continue on a study drug dose that was tolerated until completion of all study visits or until criteria to resume standard acromegaly therapy and discontinuation from the study were met. The dose of study drug used at V9/W7 remained stable through V11/W10 if tolerated. |
|
|
| OG002 | Randomized Withdrawal Period: Not Randomized | To be eligible for randomization, the subject had to have IGF-1 value ≤ULN at V10/W8 and an Investigator determination at V11/W10 that the subject tolerated the study drug. Subjects who did not meet both criteria were not to be randomized but were to be allowed to stay in the study and continue on a study drug dose that was tolerated until completion of all study visits or until criteria to resume standard acromegaly therapy and discontinuation from the study were met. The dose of study drug used at V9/W7 remained stable through V11/W10 if tolerated. |
|
|
| OG001 | Randomized Withdrawal Period: Placebo | Subjects receiving placebo during the Randomized Withdrawal Period (RWP): Eligibility for randomization into the RWP was made based on information at the V10/W8 and V11/W10. To be eligible for randomization, the participant had to have IGF-1 value ≤ULN at V10/W8 and an Investigator determination at V11/W10 that the participant tolerated the study drug. The participants were randomized at V11/W10 in a blinded manner to be switched to a placebo. |
| OG002 | Randomized Withdrawal Period: Not Randomized | To be eligible for randomization, the subject had to have IGF-1 value ≤ULN at V10/W8 and an Investigator determination at V11/W10 that the subject tolerated the study drug. Subjects who did not meet both criteria were not to be randomized but were to be allowed to stay in the study and continue on a study drug dose that was tolerated until completion of all study visits or until criteria to resume standard acromegaly therapy and discontinuation from the study were met. The dose of study drug used at V9/W7 remained stable through V11/W10 if tolerated. |
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